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Context: Hydroxypropyl-β-cyclodextrin (HPβCD) is one of the derivatized cyclodextrins most widely used as an excipient in the pharmaceutical industry, for its capacity to improve certain drugs properties. Different configurations of HPβCD are possible depending on the number and location of the 2-hydroxypropyl groups substituted on the glucose rings. Rifampicin has become the most commonly clinically used antibiotic against tuberculosis in recent years, despite its low solubility and variable bioavailability. Different techniques and materials have been proposed to enhance the properties of rifampicin: cyclodextrin complexation is one of them. The van der Waals term was the main contribution to the interaction energy, which then decisively conditioned the complex configurations. The size of rifampicin did not allow the whole molecule to fit into the host. Moreover, interaction energy was much greater when the guest was located near each rim of HPβCD, where rifampicin was partially included in the cavity and formed inclusion complexes. The piperazine tail of rifampicin was included inside the host in minimum energy structures and the guest was situated near the primary rim of HPβCD in most cases, although the complex configurations depended on the degree of substitution. Methods: A molecular mechanics simulation based on the GROMOS 53A6 force field was applied in this work to study the inclusion complexes formed by twelve configurations of HPβCD, with different degrees of substitution and rifampicin in water solution. We determined the penetration potential, the complex structures with minimum energies, the possibility of forming inclusion complexes other than those of minimum energies and potential energy surfaces. [ABSTRACT FROM AUTHOR]

In this paper, the quantum effects of fine scaling on the buckling behavior of carbon nanotubes (CNTs) under axial loading are investigated. Molecular mechanics and quantum mechanics are respectively utilized to study the buckling behavior and to obtain the molecular mechanics coefficients of fine-scale nanotubes. The results of buckling behavior of CNTs with different chiralities with finite and infinite dimensions are given, and a comparison study is presented on them. The differences between finite and infinite nanotubes reflect the quantum effects of fine scaling on the buckling behavior. In addition, the results show that the dimensional changes highly affect the mechanical properties and the buckling behavior of CNTs to certain dimensions. Moreover, dimensional changes have a significant effect on the critical buckling strain. Beside, in addition to the structure dimensions, the arrangement of structural and boundary atoms have a major influence on the buckling behavior. [ABSTRACT FROM AUTHOR]

The three-dimensional structure of DiB3, a fluorescent noncovalent complex of a genetically engineered variant of the bacterial protein lipocalin Blc with the synthetic GFP-like chromophore M739, was determined by molecular mechanics calculations. Compared to the crystal structure of the related DiB1 complex, an alternative binding site for the M739 chromophore was identified in the structure of the DiB3 complex. [ABSTRACT FROM AUTHOR]

In the present work, Pro-Gly glyproline and its biologically active complexes with heparin and with the antithrombin-heparin protein complex have been studied using molecular modelling methods. This molecule is used as a drug and exhibits antithrombotic, anticoagulant immunomodulatory, antiulcer, and antidiabetic effects. The conformational profiles of the dipeptide were studied within the molecular mechanics framework, the geometry and energy of intra- and interresidual interactions were estimated for the most stable states of the investigated dipeptide. A comparative analysis of the extended and folded structures of this molecule optimized by the DFT/B3LYP/6-31 G(d,p) method was carried out, the frontier molecular orbitals were calculated, the surface of the molecular electrostatic potential was studied, the effective charges on the atoms were determined, and the dipole moment and polarizability values were calculated. Molecular docking revealed that the folded structure of Pro-Gly glyproline showed a higher affinity value for both heparin and the antithrombin-heparin protein complex. A model of the pharmacophore of the Pro-Gly molecule for its interaction with a specific receptor was proposed. The obtained data form the basis for the development of effective analogs of glyprolines in the complex with heparin, which are more specific concerning their putative target—antithrombin. [ABSTRACT FROM AUTHOR]

The development of ideas about the 3D structure of DNA and the mechanisms of its formation, from the discovery of the double helix to the present day, is considered. Methods of modeling the 3D structure at different steps of the study of the central molecule of life are reviewed. The results of calculations of intra- and intermolecular interactions among macromolecule subunits provide grounds for the discussion of the marvelous expediency in DNA molecular structure and its adaptability to important biological functions. New data about the substantial contribution of the chemically monotonous and conformationally flexible sugar-phosphate backbone to the formation of the sequence-dependent 3D structure of DNA are presented. The conformational diversity of DNA manifests itself in both the formation of duplexes (and even triplexes or quadruplexes) with different base pair geometries and the formation of duplexes with Watson–Crick nucleoside pairs containing local conformations falling into different regions of the torsion angles of the sugar-phosphate backbone, i.e., different conformational classes. According to our calculations, these classes can be divided into two groups. One of them includes local conformations in which torsion angles are close to one of the energy minimums of the isolated elementary repeating fragment, while the second group consists of conformations where one or more of these angles deviate from that of the nearest energy minimum by more than 30°. The patterns of the formation of local 3D structures in these two groups differ significantly. [ABSTRACT FROM AUTHOR]

Using examples of an exothermic chemical reaction and self-heating of the region of a conducting filament of a memristor, heat-induced phase transitions, disadvantages of applying the classical Fourier approach on the nanoscale, and advantages of the molecular mechanics method at modeling the temperature factors are discussed. The correction for the Arrhenius relationship, taking into account the fact that the temperature becomes a random variable is proposed. Based on the introduced concepts (elementary act of heat release, as well as the distance and region of thermal impact), a methodology for taking into account the thermal factor is proposed. The correction is based on splitting the entire pool of particles into several flows, each of which corresponds to a fixed temperature value taken from a certain range. Although both continuous and discrete correction options are given, the discrete option is preferable. This is due to the fact that the methodology focuses on the application of methods of molecular mechanics, and does so intentionally in the most primitive version. The role of amorphization is noted as an example of the structural restructuring of matter in nanovolumes. It is indicated that the phonon spectra themselves, which determine heat transfer, depend on temperature. The technique is consistent with the ideology of multiscale modeling. The integral temperature increase is calculated outside the region of thermal exposure, where nonequilibrium effects are significant, by solving the standard equation of thermal conductivity. [ABSTRACT FROM AUTHOR]

Although the correlation between the regularity of micro-structures and the length of side chains has been widely reported, experiments still require precursors of polynorbornene derivatives due to the complex inter- and intra-chain interplay. This research utilizes hydrogen bonding between amide groups to design molecular models of polynorbornene derivatives (PNbs). The PNbs are abbreviated as Pm-8, where “m” indicates the amount of methylene groups as spacers in the side chain, and “8” refers to the oxyoctyl tail. The aim is to obtain a gradual variation of inter- and intra-chain interplay for further elucidation. Based on an analysis of spatial descriptors, mean square displacement (MSD), and radial distribution function (RDF) by using molecular mechanics (MM) and molecular dynamics (MD) methods, it is found that the asymmetry of side chains plays a more significant role in determining micro-structural regularity than the length. Highly asymmetric side chains are favorable for forming inter-chain hydrogen bonding, promoting interdigitation, and creating a larger scale of regularity in P8-8 and P10-8 molecules. In contrast, the relatively symmetric side chains tend to form intra-chain bonding, resulting in limited regularity within P2-8 and P4-8 molecules. Therefore, unlike regular structures that usually require symmetrical molecules, polynorbornene derivatives with asymmetric side chains have achieved highly ordered orthorhombic lattices in experiments. This study aims to offer an alternative approach to screening effective precursors of long-side chain polymers by means of semi-quantitative geometric parameters, providing a fresh perspective on the subject. Chemical structure and molecular geometry of the P8-8 model of polynorbornene derivatives (color code: purple = the main chain, red = O, white = H, gray = C) The P8-8 model of polynorbornene derivatives has an asymmetric micro-structure that promotes interdigitation of side chains, creating a larger scale of regularity in bulk structure. The name of the model is derived from the number of methylene groups as spacers and the oxyoctyl tail in the side chain, both of which are represented by the number 8.Graphical Abstract: Although the correlation between the regularity of micro-structures and the length of side chains has been widely reported, experiments still require precursors of polynorbornene derivatives due to the complex inter- and intra-chain interplay. This research utilizes hydrogen bonding between amide groups to design molecular models of polynorbornene derivatives (PNbs). The PNbs are abbreviated as Pm-8, where “m” indicates the amount of methylene groups as spacers in the side chain, and “8” refers to the oxyoctyl tail. The aim is to obtain a gradual variation of inter- and intra-chain interplay for further elucidation. Based on an analysis of spatial descriptors, mean square displacement (MSD), and radial distribution function (RDF) by using molecular mechanics (MM) and molecular dynamics (MD) methods, it is found that the asymmetry of side chains plays a more significant role in determining micro-structural regularity than the length. Highly asymmetric side chains are favorable for forming inter-chain hydrogen bonding, promoting interdigitation, and creating a larger scale of regularity in P8-8 and P10-8 molecules. In contrast, the relatively symmetric side chains tend to form intra-chain bonding, resulting in limited regularity within P2-8 and P4-8 molecules. Therefore, unlike regular structures that usually require symmetrical molecules, polynorbornene derivatives with asymmetric side chains have achieved highly ordered orthorhombic lattices in experiments. This study aims to offer an alternative approach to screening effective precursors of long-side chain polymers by means of semi-quantitative geometric parameters, providing a fresh perspective on the subject. Chemical structure and molecular geometry of the P8-8 model of polynorbornene derivatives (color code: purple = the main chain, red = O, white = H, gray = C) The P8-8 model of polynorbornene derivatives has an asymmetric micro-structure that promotes interdigitation of side chains, creating a larger scale of regularity in bulk structure. The name of the model is derived from the number of methylene groups as spacers and the oxyoctyl tail in the side chain, both of which are represented by the number 8. [ABSTRACT FROM AUTHOR]

Thymogen (L-Glutamyl-L-Tryptophan, H-Glu-Trp-OH), immunoactive dipeptide, was investigated by molecular modeling methods. The conformational profiles of this molecule were investigated by molecular mechanics method. Then obtained most stable conformations of this dipeptide were optimized using DFT/ B3LYP level of theory with 6-31+G(d,p) basis set. The structural characteristics, molecular electrostatic potential (MEP) map, highest occupied and lowest unoccupied molecular orbital energies, dipole moment (μ), polarizability (α) and other parameters characterized the molecular properties of thymogen were calculated. It was found that the conformation with extended form of backbone is optimal for this molecule. Moreover, thymogen was docking onto the specific T-cell receptor using AutoDock Vina software. It was shown that the optimized structure of thymogen calculated by DFT/B3LYP/6-31+G(d,p) gives a binding affinity value –7.9 kcal/mol, which points out that it complements well a cleft on the surface of the receptor shown to be the attachment site. On the basis of the received results the model of pharmacophore of thymogen for its interaction with T-cell receptor was proposed. [ABSTRACT FROM AUTHOR]

The design of new host–guest complexes represents a fundamental challenge in supramolecular chemistry. At the same time, it opens new opportunities in material sciences or biotechnological applications. A computational tool capable of automatically predicting the binding free energy of any host–guest complex would be a great aid in the design of new host systems, or to identify new guest molecules for a given host. We aim to build such a platform and have used the SAMPL7 challenge to test several methods and design a specific computational pipeline. Predictions will be based on machine learning (when previous knowledge is available) or a physics-based method (otherwise). The formerly delivered predictions with an RMSE of 1.67 kcal/mol but will require further work to identify when a specific system is outside of the scope of the model. The latter is combines the semiempirical GFN2B functional, with docking, molecular mechanics, and molecular dynamics. Correct predictions (RMSE of 1.45 kcal/mol) are contingent on the identification of the correct binding mode, which can be very challenging for host–guest systems with a large number of degrees of freedom. Participation in the blind SAMPL7 challenge provided fundamental direction to the project. More advanced versions of the pipeline will be tested against future SAMPL challenges. [ABSTRACT FROM AUTHOR]

A reliable method for molecular structure determination, excluding single-crystal X-ray diffraction (SCXRD), has been applied to six methyl glycoside tetrabenzoates. The proposed method is based on a global conformational search using molecular mechanics and subsequent DFT calculations guided by a solid-state NMR experiment. The accuracy of the applied method has been verified on three methyl glycoside benzoates for which the SCXRD analysis has been completed. It appeared that the calculated conformations of unprivileged energy could be found in the solid state. Bulky substituents (benzoates) exerted less energetically favored interactions in crystals in contrast to isolated molecules. Therefore, solid-state NMR was revealed to be an indispensable approach for choosing credible conformations from the calculated conformations. [ABSTRACT FROM AUTHOR]

Application of a small radius of the hydrogen atom in molecular-mechanical models of hydrogen bonding improves the estimate of the solvation free energy of organic substances. At the same time, the density and evaporation heat of the bulk water vary slightly and are close to experimental values. Blind testing drug candidates in the SAMPL6 simulation competition showed that using the same Lennard-Jones hydrogen parameters for the hydroxyl, hydroxycarbonyl, amino, and amide groups is enough to predict log P octanol–water with MAE 0.67 and RMSD 0.75. [ABSTRACT FROM AUTHOR]

Difurfuryl disulfide has been widely used as a flavor compound or a pharmaceutical substance. Encapsulation can provide protection and enhance the stability of the entrapped ingredients, while formation of inclusion complex is one of the methods for encapsulation. In this paper, difurfuryl disulfide-β-cyclodextrin inclusion complex was prepared with difurfuryl disulfide as guest and β-cyclodextrin (β-CD) as host respectively. The inclusion complex was characterized by optical microscope, Fourier-transform infrared spectroscopy (FTIR) and thermo gravity analysis. The characteristics and kinetics of difurfuryl disulfide release from the inclusion complex were investigated. Geometries of the inclusion complex were optimized and the binding energies were obtained using molecular mechanics (MM) calculations. The results show that most of the difurfuryl disulfide-β-CD inclusion complexes, with parallelogram, trapezoidal and rhombic shapes, are in the size range of 1 to 5 µm. The difurfuryl disulfide loading capacity is about 19.8% and the molar ratio of difurfuryl disulfide to β-CD for the inclusion complex is approximately 1:1. The FTIR band at 3380 cm−1 of β-CD is blue-shifted after formation of difurfuryl disulfide-β-CD inclusion complex, and a new band appears at 1500 cm−1 in the FTIR of the inclusion complex while the band is absent in the FTIR curve β-CD. Difurfuryl disulfide release characteristics from its inclusion complex with the increase of temperature were obtained by thermo gravity analysis. Difurfuryl disulfide release kinetic parameters (reaction order, activation energy, pre-exponential factor) were calculated. The results of MM2 calculations indicates that the minimum binding energy is − 135.2 kJ/mol when Z coordinate of S1 is 3.7 × 10−10 m. The most stable structure of the inclusion complex was obtained. [ABSTRACT FROM AUTHOR]

Complete understanding of the role of mechanical forces in biological processes requires knowledge of the mechanical properties of individual proteins and living cells. Moreover, the dynamic response of biological systems at the nano- and microscales span over several orders of magnitude in time, from sub-microseconds to several minutes. Thus, access to force measurements over a wide range of length and time scales is required. High-speed atomic force microscopy (HS-AFM) using ultrashort cantilevers has emerged as a tool to study the dynamics of biomolecules and cells at video rates. The adaptation of HS-AFM to perform high-speed force spectroscopy (HS-FS) allows probing protein unfolding and receptor/ligand unbinding up to the velocity of molecular dynamics (MD) simulations with sub-microsecond time resolution. Moreover, application of HS-FS on living cells allows probing the viscoelastic response at short time scales providing deep understanding of cytoskeleton dynamics. In this mini-review, we assess the principles and recent developments and applications of HS-FS using ultrashort cantilevers to probe molecular and cellular mechanics. [ABSTRACT FROM AUTHOR]

Pectin–curcumin composite was synthesized in a reaction mediated by dicyclohexylcarbodiimide and dimethylaminopyridine. The formation of pectin–curcumin composite was confirmed by FTIR and NMR spectral analyses. The results of differential scanning calorimetry, X-ray diffraction and scanning electron microscopy studies established that the composite is amorphous in nature. The curcumin contents in the composite were found to be 384.39 μg/g of the composite. The critical aggregation concentration determined by fluorescence spectroscopy and dynamic light scattering technique was found to be in the range of 140–180 μg/mL. The results of in silico molecular mechanistic simulations of the interaction between pectin and curcumin revealed the stability of pectin–curcumin composite, which favored its formation. In vitro release study showed 93% (pH 1.2) and 46% (pH 7.4) of curcumin getting released in 48 h. Further, the release of curcumin from the composite followed first-order (pH 1.2) and zero-order (pH 7.4) kinetics, with anomalous release mechanism. Further, the results of cytotoxicity studies showed a significantly higher inhibition of KYSE-30 cell lines by composite over curcumin. Thus, coupling of curcumin to pectin improves its therapeutic delivery and efficacy. [ABSTRACT FROM AUTHOR]

Any mechanical modeling of matter depends primarily on the chosen spatial and temporal observation scales. Roughly speaking, there are three such scales, microscopic for quantum, mesoscopic for statistical, and macroscopic for continuum mechanics. This by itself demands for adequate scale-bridging procedures. This paper focuses on the passage from molecular to continuum formulations of the basic balance laws of linear momentum and energy, kinetic, internal, and total. The procedure used is a modification of that introduced by Irving & Kirkwood (J. Chem. Phys. 18(6):817–829, 1950), as improved by Noll (Indiana Univ. Math. J. 4:627–646, 1955); alternative procedures are mentioned. The proposed modification consists primarily in equipping provisionally the target continuum balances with internal-source terms accounting at the macroscopic scale for microscopic motion randomness, when, e.g., a loosely aggregated material system evolves at relatively high temperature. Attention is also devoted to those continuum notions that either are hardly given a universally accepted molecular counterpart or even cannot and ultimately need not be given one, such as the notion of material point. [ABSTRACT FROM AUTHOR]

Walter Noll (1925–2017) was an American mathematician of German birth who made lasting contributions to the foundations of continuum physics and the classical non-linear field theory. This essay is an attempt to put in a broader perspective Noll's methods and achievements in the hope that young generations of researchers may find their inspiration in the talent and depth of the old. By no means should this be considered as a historical account on the development of continuum mechanics through the second half of the twentieth century. We are content to illuminate Noll's precious legacy. [ABSTRACT FROM AUTHOR]

Some difficulties in the application of various methods of computer modeling for the study of regularities of formation of spatial structure of DNA are analyzed. Computations of intermolecular interaction energy for all ten pairwise combinations of methylated bases (1-methylpyrimidines and 9-methylpurines) in various mutual base positions were performed due to the important role of nitrous bases. Local energy minima that correspond to different mutual positions of the molecules have been found using different molecular mechanics force fields, ab initio quantum mechanics, and density functional theory. The energy minima that correspond to three types of mutual molecule positions, namely, (1) base positions with two N–H...O and/or N–H...N hydrogen bonds; (2) nearly parallel arrangements of base ring planes, that is, base stacking; and (3) T-shaped (nearly perpendicular) base ring positions and hydrogen bond formation were extensively studied. The majority of these minima were obtained using methods of different complexities; however, the method of calculation determines which minimum is the deepest (global) for certain base combination and relative depths of various minima. Analysis of these simulations and of the computations on simple DNA fragments, as well as of extensive data from the literature suggests that there has been no method suitable for quantitative description of all the experimental data on non-bonded interactions in DNA. The comparison of energy and structure characteristics of the complexes calculated by various methods demonstrates their abilities and shortcomings. A valid description of non-bonded interactions of nucleic acids requires additional investigations of their simple fragments and the combined use of various methods. [ABSTRACT FROM AUTHOR]

In this perspective, we review the theory and methodology of the derivation of force fields (FFs), and their validity, for molecular simulations, from their inception in the second half of the twentieth century to the improved representations at the end of the century. We examine the representations of the physics embodied in various force fields, their accuracy and deficiencies. The early days in the 1950s and 60s saw FFs first introduced to analyze vibrational spectra. The advent of computers was soon followed by the first molecular mechanics machine calculations. From the very first papers it was recognized that the accuracy with which the FFs represented the physics was critical if meaningful calculated structural and thermodynamic properties were to be achieved. We discuss the rigorous methodology formulated by Lifson, and later Allinger to derive molecular FFs, not only obtain optimal parameters but also uncover deficiencies in the representation of the physics and improve the functional form to account for this physics. In this context, the known coupling between valence coordinates and the importance of coupling terms to describe the physics of this coupling is evaluated. Early simplified, truncated FFs introduced to allow simulations of macromolecular systems are reviewed and their subsequent improvement assessed. We examine in some depth: the basis of the reformulation of the H-bond to its current description; the early introduction of QM in FF development methodology to calculate partial charges and rotational barriers; the powerful and abundant information provided by crystal structure and energetic observables to derive and test all aspects of a FF including both nonbond and intramolecular functional forms; the combined use of QM, along with crystallography and lattice energy calculations to derive rotational barriers about ɸ and ψ; the development and results of methodologies to derive "QM FFs" by sampling the QM energy surface, either by calculating energies at hundreds of configurations, or by describing the energy surface by energies, first and second derivatives sampled over the surface; and the use of the latter to probe the validity of the representations of the physics, reveal flaws and assess improved functional forms. Research demonstrating significant effects of the flaws in the use of the improper torsion angle to represent out of plane deformations, and the standard Lorentz-Berthelot combining rules for nonbonded interactions, and the more accurate descriptions presented are also reviewed. Finally, we discuss the thorough studies involved in deriving the 2nd generation all-atom versions of the CHARMm, AMBER and OPLS FFs, and how the extensive set of observables used in these studies allowed, in the spirit of Lifson, a characterization of both the abilities, but more importantly the deficiencies in the diagonal 12-6-1 FFs used. The significant contribution made by the extensive set of observables compiled in these papers as a basis to test improved forms is noted. In the following paper, we discuss the progress in improving the FFs and representations of the physics that have been investigated in the years following the research described above. [ABSTRACT FROM AUTHOR]

In the previous paper, we reviewed the origins of energy based calculations, and the early science of FF development. The initial efforts spanning the period from roughly the early 1970s to the mid to late 1990s saw the development of methodologies and philosophies of the derivation of FFs. The use of Cartesian coordinates, derivation of the H-bond potential, different functional forms including diagonal quadratic expressions, coupled valence FFs, functional form of combination rules, and out of plane angles, were all investigated in this period. The use of conformational energetics, vibrational frequencies, crystal structure and energetics, liquid properties, and ab initio data were all described to one degree or another in deriving and validating both the FF functional forms and force constants. Here we discuss the advances made since in improving the rigor and robustness of these initial FFs. The inability of the simple quadratic diagonal FF to accurately describe biomolecular energetics over a large domain of molecular structure, and intermolecular configurations, was pointed out in numerous studies. Two main approaches have been taken to overcome this problem. The first involves the introduction of error functions, either exploiting torsion terms or introducing explicit 2-D error correction grids. The results and remaining challenges of these functional forms is examined. The second approach has been to improve the representation of the physics of intra and intermolecular interactions. The latter involves including descriptions of polarizability, charge flux aka geometry dependent charges, more accurate representations of spatial electron density such as multipole moments, anisotropic nonbond potentials, nonbond and polarization flux, among others. These effects, though not as extensively studied, likely hold the key to achieving the rigorous reproduction of structural and energetic properties long sought in biomolecular simulations, and are surveyed here. In addition, the quality of training and validation observables are evaluated. The necessity of including an ample set of energetic and crystal observables is emphasized, and the inadequacy of free energy as a criterion for FF reliability discussed. Finally, in light of the results of applications of the two approaches to FF development, we propose a "recipe" of terms describing the physics of inter and intramolecular interactions whose inclusion in FFs would significantly improve our understanding of the energetics and dynamics of biomolecular systems resulting from molecular dynamics and other energy based simulations. [ABSTRACT FROM AUTHOR]

The force constants related to the bond stretching and angular variation of boron nitride, silicon carbide, aluminium nitride and gallium nitride nanosheets are directly evaluated from ab-initio reference solutions of the Young’s modulus and the Poisson’s ratio. To this end, the analytical expressions of the elastic constants of a generic monolayer hexagonal diatomic sheet are derived, starting from its sticks-and-springs molecular mechanics model, through proper tools of the homogenization of periodic discrete media. Numerical benchmark assessments are given. [ABSTRACT FROM AUTHOR]

Clusters simulating the formation of Gd(III) stearate complex monolayers on the surface of an aqueous phase are studied by means of molecular mechanics. From a comparison of the calculated and experimental data, it concluded that Langmuir monolayers are produced by Gd(III) aqua complexes with one and two stearate anions. [ABSTRACT FROM AUTHOR]

In the paper we review the application of two techniques (molecular mechanics and quantum mechanics) to study the influence of geometry optimization of the steroid sulfatase inhibitors on the values of descriptors coded their chemical structure and their free binding energy with the STS protein. We selected 22 STS-inhibitors and compared their structures optimized with MM+, PM7 and DFT B3LYP/6-31++G* approaches considering separately the bond lengths, angles, dihedral angles and total energies. We proved that different minimum energy conformers could be generated depending on the choice of the optimization method. However, the results indicated that selection of the geometry optimization method did not affect the optimal STS inhibitor coordinates, and hence the values of molecular descriptors which describe the 3D structure of the molecule. To study the interaction pattern of the STS inhibitors (optimized using different methods) with the target receptor we applied two strategies: AutoDock and PathDock. The docking studies point out that selection of software to docking simulation is one of the crucial factors determining the binding mode of STS inhibitors with their molecular target. Other factor is related to the ligand orientation in the binding pocket. Finally, obtained results indicate that MM+ and PM7 methods (faster and less expensive) could be successfully employed to geometry optimization of the STS inhibitors before their docking procedure as well as for molecular descriptors calculations. [ABSTRACT FROM AUTHOR]

Quantum-chemical simulation of the ground state [the density function B3LYP/6-31G, B3LYP/6-31G(d), and B3LYP/6-31+G(d,p) and the perturbation theory MP2/6-31G(d) methods] and the transition states [the B3LYP/6-31G(d) method] of 4,4′-methoxypropylstilbene molecule has been performed. Using the Ellinger MM2 force field method, the potentials of internal rotation have been obtained for each rotational degree of freedom of the molecule. The B3LYP simulation has revealed the planarity of the conjugated system and the orthogonal position of the alkyl substituent, whereas the benzene rings have deviated by about 20° with respect to the double bond plane according to the MP2 data. Three transition states of the molecule corresponding to the saddle points of the first and the second orders have been revealed. The stationary points have been identified by means of vibrational analysis. [ABSTRACT FROM AUTHOR]

The majority of computer simulations exploring biomolecular function employ Class I additive force fields (FF), which do not treat polarization explicitly. Accordingly, much effort has been made into developing models that go beyond the additive approximation. Development and optimization of the Drude polarizable FF has yielded parameters for selected lipids, proteins, DNA and a limited number of carbohydrates. The work presented here details parametrization of aliphatic aldehydes and ketones (viz. acetaldehyde, propionaldehyde, butaryaldehyde, isobutaryaldehyde, acetone, and butanone) as well as their associated acyclic sugars ( d-allose and d-psicose). LJ parameters are optimized targeting experimental heats of vaporization and molecular volumes, while the electrostatic parameters are optimized targeting QM water interactions, dipole moments, and molecular polarizabilities. Bonded parameters are targeted to both QM and crystal survey values, with the models for ketones and aldehydes shown to be in good agreement with QM and experimental target data. The reported heats of vaporization and molecular volumes represent a compromise between the studied model compounds. Simulations of the model compounds show an increase in the magnitude and the fluctuations of the dipole moments in moving from gas phase to condensed phases, which is a phenomenon that the additive FF is intrinsically unable to reproduce. The result is a polarizable model for aliphatic ketones and aldehydes including the acyclic sugars d-allose and d-psicose, thereby extending the available biomolecules in the Drude polarizable FF. [ABSTRACT FROM AUTHOR]

In this paper, the geometry of single-walled carbon nanotubes without any external loading is analyzed via an energy procedure. The nanotube is assumed to be inscribed into a perfect cylinder of unknown diameter, which is estimated by minimizing the total interatomic potential involved into a basic cell with several carbon atoms and their corresponding bonds. In this step, two interatomic potentials have been adopted in order to compare their influence on the obtained results. Our calculations show that the widely used conformal mapping is not the most suitable option to reproduce the geometry of single-walled nanotubes in absence of external loading. Likewise, a more accurate method to estimate the initial diameter of the nanotube is developed, yielding higher differences with smaller nanotubes in comparison with other published works. The present analysis can be useful in the framework of molecular mechanics or continuum models as an alternative way to introduce initial stresses (due to the curvature of the cylinder) in the mechanical analysis, against other involved methods. [ABSTRACT FROM AUTHOR]

A series of N-phenylthiourea derivatives was built starting from the X-ray structure in the molecular mechanics framework and the interaction profile in the complex with the catechol oxidase was traced using molecular dynamics simulation. The results showed that the geometry and interactions between ligand and receptor were highly related to the position of the substituted side chains of phenyl moiety. At the end of molecular dynamics run, a concentrated multicenter hydrogen bond was created between the substituted ligand and receptor. The conformation of the ligand itself were also restricted in the receptor pocket. Furthermore, the simulation time of 50 ns were found to be long enough to explore the relevant conformational space and the stationary behavior of the molecular dynamic could be observed. [ABSTRACT FROM AUTHOR]

Analytical solutions for the elastic properties of a variety of binary nanotubes with arbitrary chirality are obtained through the study of systematic molecular mechanics. This molecular mechanics model is first extended to chiral binary nanotubes by introducing an additional out-of-plane inversion term into the so-called stick-spiral model, which results from the polar bonds and the buckling of binary graphitic crystals. The closed-form expressions for the longitudinal and circumferential Young's modulus and Poisson's ratio of chiral binary nanotubes are derived as functions of the tube diameter. The obtained inversion force constants are negative for all types of binary nanotubes, and the predicted tube stiffness is lower than that by the former stick-spiral model without consideration of the inversion term, reflecting the softening effect of the buckling on the elastic properties of binary nanotubes. The obtained properties are shown to be comparable to available density functional theory calculated results and to be chirality and size sensitive. The developed model and explicit solutions provide a systematic understanding of the mechanical performance of binary nanotubes consisting of III-V and II-VI group elements. [ABSTRACT FROM AUTHOR]

A molecular structural mechanics (MSM) method has been implemented to investigate the free vibration of microtubules (MTs). The emphasis is placed on the effects of the configuration and the imperfect boundaries of MTs. It is shown that the influence of protofilament number on the fundamental frequency is strong, while the effect of helix-start number is almost negligible. The fundamental frequency is also found to decrease as the number of the blocked filaments at boundaries decreases. Subsequently, the Euler-Bernoulli beam theory is employed to reveal the physics behind the simulation results. Fitting the Euler-Bernoulli beam into the MSM data leads to an explicit formula for the fundamental frequency of MTs with various configurations and identifies a possible correlation between the imperfect boundary conditions and the length-dependent bending stiffness of MTs reported in experiments. [ABSTRACT FROM AUTHOR]

Complete replacement of aromatic carbon bonds in graphene by carbyne chains gives rise to supergraphene whose mechanical properties are expected to depend on its structure. However, this dependence is to date unclear. In this paper, explicit expressions for the in-plane stiffness and Poisson's ratio of supergraphene are obtained using a molecular mechanics model. The theoretical results show that the in-plane stiffness of supergraphene is drastically (at least one order) smaller than that of graphene, whereas its Poisson's ratio is higher than 0.5. As the index number increases (i.e., the length of carbyne chains increases and the bond density decreases), the in-plane stiffness of supergraphene decreases while the Poisson's ratio increases. By analyzing the relation among the layer modulus, in-plane stiffness and Poisson's ratio, it is revealed that the mechanism of the faster decrease in the in-plane stiffness than the bond density is due to the increase of Poisson's ratio. These findings are useful for future applications of supergraphene in nanomechanical systems. [ABSTRACT FROM AUTHOR]

The axial modulus of the cellulose Iβ crystal is as high as 120-160 GPa. The importance of hydrogen bonds is often emphasized in this context, although intrinsic stiffness of the hydrogen bonds is relatively low. Here, hydrogen bond-covalent bond synergies are investigated quantitatively using molecular mechanics and molecular dynamics simulations for the so-called leverage effect, a model introduced recently in which strains for intra-molecular hydrogen bonds are higher than for the cellulose chain as a whole, thereby amplifying their contribution to the total stiffness. The present work also includes simulation of the hydrogen bonding band shifts in vibrational spectra during cellulose deformation, which are compared with FT-IR data. The leverage effect hypothesis was supported by the results, although the total contribution to cellulose stiffness is only 12 %. Hydrogen bonding is still critically important and would lower the modulus much more than 12 %, if 'artificially' removed in the model. The reason is that intra-molecular hydrogen bonding preserves the crystal structure and directs axial deformation mechanisms towards higher energy deformation and high stiffness. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is the first growth factor receptor proposed as a target for cancer therapy. Molecular modeling protocols like molecular docking, molecular mechanics/generalized born surface area (MM/GBSA) calculations and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on 45 molecules to understand the structural requirements for EGFR tyrosine kinase inhibitors. Conformation for all the molecules obtained from molecular docking were used as is for 3D-QSAR analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were obtained by performing partial least square analysis on 35 training molecules and these models were validated using 10 test moleucles. The models showed good statistical results in terms of r , q $^{2}_{\text {loo}}$ and r $^{2}_{\text {pred}}$ values. Information rendered from 3D-QSAR model and sitemap analysis was used to optimize lead molecule to design prospective inhibitors. Improvement in EGFR binding affinity can be achieved by substitutional modification on phenyl ring attached to alkynyl group with bulkier hydrogen bond donor and acceptor substituents that can increase favourable interaction with the receptor. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We present a novel scheme to derive nonlinearly elastic constitutive laws for special Cosserat rod modeling of nano and continuum rods. We first construct a 6-parameter (corresponding to the six strains in the theory of special Cosserat rods) family of helical rod configurations subjected to uniform strain along their arc-length. The uniformity in strain then enables us to deduce the constitutive laws by just solving the warping of the helical rod's cross-section (smallest repeating cell for nanorods) but under certain constraints. The constraints are shown to be critical in the absence of which, the 6-parameter family reduces to a well known 2-parameter family of uniform helical equilibria. An explicit formula for the 6-parameter helical map is derived which maps atoms in the repeating cell of a nanorod to their images for the purpose of repeating cell energy minimization. A scheme for the passage from nano to continuum scale is also presented to derive the constitutive laws of a continuum rod via atomistic calculations of nanorods. The bending, twisting, stretching and shearing stiffnesses of diamond nanorods and carbon nanotubes are computed to demonstrate our theory. We show that our scheme is more general and accurate than existing schemes allowing us to deduce shearing stiffness and several coupling stiffnesses of a nanorod for the first time. [ABSTRACT FROM AUTHOR]

A new all-atom first-principles force field (FF) is constructed for the bimetallic, four-bladed zinc paddlewheel (ZPW) motif. Zinc-ligand interactions are described via Morse functions and the angular geometry at the metal centers is modeled with a pure ligand-ligand repulsion term. The ZPW-FF is principally based on 15 DFT-optimized model systems of general formula ZnPR.nL, where ZnP is the base Zn2(O2CR)4 unit, R=H, CH3 or CF3, L=NH3 or pyridine, and n = 0, 1 or 2. It correctly generates the distorted tetrahedral coordination of the uncapped [Zn2(O2CR)4] species in their ground states as well as giving reasonable structures and energies for the higher symmetry D4h transition state conformations. The zinc-ligand Morse function reference distance, r0, is further refined against 30 complexes located in the Cambridge Structural Database and this FF is applied to pore models of t h e f l e x i b l e me t a l - o rganic framework (MOF) [Zn(bdc)2(dabco)]n (bdc = 1,4-benzendicarboxylate; dabco =1,4-diazabicyclo(2.2.2)octane). A single pore model reproduces the unit cell of the evacuated MOF system while a 3×3 grid model is necessary to provide good agreement with the observed pronounced structural changes upon adsorption of either dimethylformamide or benzene. [ABSTRACT FROM AUTHOR]

It is generally accepted that important features of the Watson-Crick duplex (WCD) originate from the molecular structure of its subunits. However, it is still unclear what properties of each subunit are responsible for significant features of the WCD structure. Computations of deoxydinucleoside monophosphate (dDMP) complexes with Na ions on the basis of the density functional theory (DFT) have shown that conformational properties of minimal single-stranded fragments of DNA play a pivotal role in the origin of the unique features of the WCD. The directionality of the sugar-phosphate backbone (SPB) and preferable ranges of its torsion angles combined with the difference in geometry between purines and pyrimidines have been found to define the nucleotide sequence dependence of the WCD three-dimensional structure. In this work, density functional theory computations were extended to minimal duplex fragments, that is, complementary dDMP (cdDMP) complexes with Na ions. Using several computational methods and various functionals, energy minima were searched for the BI conformation of cdDMP complexes with different nucleotide sequences. Two sequences were optimized using an ab initio method at the MP2/6-31++G** level of theory. An analysis of the SPB torsion angles, sugar-ring puckering, and mutual base positions in the optimized structures showed that the conformational features of cdDMP complexes with Na ions remained within the BI ranges and become more similar to the corresponding features that WCDs display in a crystal. Qualitatively, the main features of each cdDMP complex were invariant with different computational methods, although the values of certain conformational parameters could vary, but still within the limits that are typical of the corresponding family. Common functionals that are employed in DFT calculations were observed to overestimate the distance between base pairs, while MP2 computations and new complex functionals yielded structures with atom-atom contacts that are too close. Several energy minima that correspond to the BI conformation have been proven to exist for certain cdDMP complexes with Na ions, indicating that the topography of the potential energy surface is complex. This circumstance accounts for the variation of conformational parameters among duplex fragments with the same nucleotide sequence. The common AMBER and CHARMM molecular mechanics force fields reproduce many conformational characteristics of dDMPs and their complementary complexes with Na ions, but fail to reproduce certain details of the nucleotide sequence dependence of the WCD conformation. [ABSTRACT FROM AUTHOR]

The paper deals with the comparison of different theoretical methods for the calculation of stabilization energies of glycosyl cations from fucofuranoside glycosyl donors containing different protecting groups at atom O(3). The experimental and calculated data on stereoselectivity of glycosylation were compared. The formation of the stabilized glycosyl cations is considered as one of the possible steps of glycosylation reaction, which exerts influence on the stereoselectivity of the process and makes it possible to obtain difficultly accessible 1,2- cis-glycosides. Semi-empirical and ab initio methods without allowance for the electron correlation underestimate the stabilization energy values. The allowance for the electron correlation in the MP2 approximation, as well as the calculations by density functional theory, allowed us to obtain the data corresponding to the experimentally observed stereoselectivity. [ABSTRACT FROM AUTHOR]

Complexation of morniflumate hydrochloride (MOR) with β-cyclodextrin (β-CD) in aqueous solution was studied. Structure of the MOR-β-CD inclusion complex was obtained by a combination of H NMR and molecular modeling studies. Computational models obtained by molecular mechanics and molecular dynamics were analyzed for their atom-accuracy. ROESY crosspeak intensities calculated from intermolecular interproton distances were compared with experimental intensities. The results demonstrate that comparison of calculated and experimental intensities is a good criterion to determine accuracy of the structure of CD complexes. Moreover, it is also demonstrated that ROESY experiment, with longer mixing time when initial rate approximation condition is not valid, can be used for quantitative purpose if intensity ratios, instead of absolute intensities, are used. [ABSTRACT FROM AUTHOR]

Encapsulation aims at protecting components, providing controlled release, preventing oxidation and extending the shelf life. The inclusion complex of citral and monochlorotriazinyl-β-cyclodextrin has been studied. The scanning electron microscopy result showed that the dried citral-monochlorotriazinyl-β-cyclodextrin inclusion complexes formed aggregates with many geometric shapes in the size range 1-2 μm, and the transmission electron microscopy result shows that the inclusion complex aggregates were expressed through a bicontinuous 'worm-type' pore system. Fourier transform infrared spectroscopy results show that citral enters the cavity of monochlorotriazinyl-β-cyclodextrin. The citral loading capacity determined from thermogravimetric data is about 8.96 %, and a 1:1 stoichiometry is obtained. Pyrolysis characteristics of the inclusion complexes were determined. Geometries of host, guest and the host-guest inclusion complex were optimized using molecular mechanics calculations. The binding energies for the most stable complexes geranial/monochlorotriazinyl-β-cyclodextrin and neral/monochlorotriazinyl-β-cyclodextrin are −143 and −162 kJ mol, respectively. The shapes and orientations of those complexes were presented. [ABSTRACT FROM AUTHOR]

Molecular mechanics based finite element analysis is adopted in the current work to evaluate the mechanical properties of Zigzag, Armchair and Chiral Single wall Carbon Nanotubes (SWCNT) of different diameters and chiralities. Three different types of atomic bonds, that is Carbon-Carbon covalent bond and two types of Carbon-Carbon van der Waals bonds are considered in the carbon nanotube system. The stiffness values of these bonds are calculated using the molecular potentials, namely Morse potential function and Lennard-Jones interaction potential function respectively and these stiffness's are assigned to spring elements in the finite element model of the CNT. The geometry of CNT is built using a macro that is developed for the finite element analysis software. The finite element model of the CNT is constructed, appropriate boundary conditions are applied and the behavior of mechanical properties of CNT is studied. [ABSTRACT FROM AUTHOR]

Graphene sheets are excellent materials to be adopted for powerful applications because of their superior mechanical and electrical properties. This study proposes a multilayered graphene sheet (MLGS) through finite element model (FEM) based on the use of hybrid of beam and spring elements and evaluate its mechanical properties with different gap thicknesses. A three-dimensional coupled FEM for an MLGS is developed through molecular mechanics. The interaction forces of the graphene layer with different gap thicknesses are also considered. The out-of-plane deformation of the bonds is distinguished from the in-plane deformation by considering a circular cross section for the beam elements. The effects of the interlayer forces on Young's modulus and shear modulus of MLGS are investigated. Simulation results from this work are comparable to both experimental tests and numerical studies from literature. [ABSTRACT FROM AUTHOR]

The elastic and fracture properties of both two-dimensional graphene and three-dimensional graphite were calculated based on molecular mechanics method, including the atomic bonding (stretching and bending) and non-bonding (van der Waal) energies. Since graphene and graphite are periodically arranged atomic structures, the representative unit cell could be chosen to illustrate their deformations under uniform loadings. The carbon bond length and angle changes of the graphene/graphite as well as the interlayer distance variations of the graphite under various loading conditions could be realized numerically under the geometry constraints and minimum energy assumption. It was found that the mechanical properties of graphene/graphite demonstrated distinct directional dependences at small and large deformations. In elastic region, graphene was in-plane isotropic, while graphite was transversely isotropic with the symmetry axis along out-of-plane direction. Meanwhile, the in-plane deformation of the representative unit cell was not uniform along armchair direction due to the discrete and non-uniform distributions of the atoms. The fracture of graphene/graphite could be predicted based on critical bond length criteria. It was noticed that the fracture behavior were directional dependent, and the fracture strain under simple tension was lower while loading on zigzag edge of graphene/graphite, which was consistent with molecular dynamics simulation results. [ABSTRACT FROM AUTHOR]

The present work investigates Young's modulus of hexagonal monolayer sheets based on molecular mechanics. A repeating unit cell of the sheet has been chosen. Harmonic force field is adopted to model atomic interactions. The total energy of the unit cell is established as a function of the force constants and atomic displacements. A closed-form expression is formulated for Young's modulus of the sheet by minimizing the total energy of the unit cell under uniaxial tension in equilibrium state. Molecular dynamics simulations were also carried out to consider Young's modulus of graphene, boron nitride, silicon carbide, aluminum nitride, and boron antimonide monolayer sheets. The accuracy of the proposed formula is verified and discussed with results obtained by molecular dynamics simulations and available data in the literature for these 5 sheets. [ABSTRACT FROM AUTHOR]

The structural aspects of the complexation of ( R)- and ( S)-benzhexol with β-cyclodextrin (β-CD) were explored using quantitative rotating-frame overhauser effect spectroscopy (ROESY) analysis and molecular mechanics (MM) and molecular dynamics (MD) simulations. Several modes of penetration of phenyl ring, studied by MM2 minimizations, confirmed preference for wide side entry. MD simulations were performed through wider side only and interproton distances between phenyl ring of benzhexol (BEN) and β-CD cavity obtained from lowest energy structures were used to calculate relative ROESY peak intensities. The structures for which calculated intensities were found in better agreement with experimental were then fine-tuned to obtain proposed structures. The results show that highly symmetrical cyclodextrin should be used for computational studies and kept static throughout the simulation. The energy should not be taken as the only criterion for final selection but a comparison of calculated ROESY intensity ratios with experimental ratios is better. The results also imply that ROESY peak intensity ratios can be used for quantitative purposes even with higher mixing time. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We present an extension of the AMOEBA force field to several common organic heterocycles, namely pyridine, pyrazine, pyrimidine, pyridazine, the three unique triazines, and the two unique tetrazines. Atomic multipoles for newly defined atom types were obtained from quantum chemical calculations on the isolated molecules. Atomic polarizability parameters are maintained at their standard AMOEBA values for corresponding atomic classes while standard van der Waals parameters are rescaled to reproduce CCSD(T) intermolecular interaction energies of selected dimer structures. In order to improve vibrational frequencies that are important both spectroscopically and for flexible dynamics, parameters for covalent terms, i.e., bond-stretching, angle-bending, and stretch-bend terms, were optimized and added to the existing AMOEBA force field. We validate our force field through comparison of molecular structural, vibrational, electrostatic, and energetic properties—including intermolecular interaction energies—to reliable quantum chemical data for the various systems of interest. [ABSTRACT FROM AUTHOR]

The aim of this paper was to develop a structural mechanics (SM) model for the microtubules (MTs) in cells. The technique enables one to study the configuration effect on the mechanical properties of MTs and enjoys greatly improved computational efficiency as compared with molecular dynamics simulations. The SM model shows that the Young's modulus has nearly a constant value around 0.83 GPa, whereas the shear modulus, two orders of magnitude lower, varies considerably with the protofilament number $$N$$ and helix-start number $$S$$ . The dependence of the bending stiffness and persistence length on the MT length and protofilament number $$N$$ is also examined and explained based on the continuum mechanics theories. Specifically, the SM model is found to be in good agreement with available simulation and experiment results, showing its robustness in studying the static deformation of MTs and the potential for characterizing the buckling and vibration of MTs as well as the mechanical behaviour of intermediate and actin filaments. [ABSTRACT FROM AUTHOR]

This article discusses the vibrational properties of silicon carbide nanotubes with various dimensions, chiralities and boundary conditions. The molecular mechanics-based finite element method is applied to study the mode shapes and natural frequencies of the silicon carbide nanotubes. The results reveal that the natural frequencies of the nanotubes increase with decreasing length, but they do not show monotone behaviors vs. diameter changes. The reasons are discussed in detail. [ABSTRACT FROM AUTHOR]

The objective of the present study is to model the analogues of monosialoganglioside (GM3) by making modifications in its sialic acid residue with different substitutions in aqueous environment and to determine their structural stability based upon computational molecular dynamics. Molecular mechanics and molecular dynamics investigation was carried out to study the conformational preferences of the analogues of GM3. Dynamic simulations were carried out on the analogues of GM3 varying in the substituents at C-1, C-4, C-5, C-8 and C-9 positions of their sialic acid or Neuraminic acid (NeuAc) residue. The analogues are soaked in a periodic box of TIP3P water as solvent and subjected to a 10 ns molecular dynamics (MD) simulation using AMBER ff03 and gaff force fields with 30 ps equilibration. The analogue of GM3 with 9- N-succNeuAc (analogue5, C9 substitution) was observed to have the lowest energy of −6112.5 kcal/mol. Graphical analysis made on the MD trajectory reveals the direct and water mediated hydrogen bonds existing in these sialic acid analogues. The preferable conformations for glycosidic linkages of GM3 analogues found in different minimum energy regions in the conformational maps were identified. This study sheds light on the conformational preferences of GM3 analogues which may be essential for the design of GM3 analogues as inhibitors for different ganglioside specific pathogenic proteins such as bacterial toxins, influenza toxins and neuraminidases. [ABSTRACT FROM AUTHOR]

The present work investigates Young's modulus of hexagonal nanosheets and nanotubes based on dimensional analysis and molecular mechanics. Using second derivatives of the strain energy density revealed from molecular dynamics simulations at 0 K (i.e., molecular mechanics) with harmonic potentials for various combinations of force constants, Young's modulus have been computed for single-walled armchair and zigzag nanotubes of different radii. This parametric study with the aid of dimensional analysis allows explicitly establishing Young's modulus of ( n, n) armchair and ( n, 0) zigzag nanotubes as functions of the force constants, bond length and chiral index n. Proposed formulae are applied to estimate Young's modulus of graphene, boron nitride, silicon carbide sheets and their nanotubes. The accuracy of the proposed formulae are verified and discussed with available data in the literature for these three sheets and their nanotubes. [ABSTRACT FROM AUTHOR]

Recent biochemical experiments have revealed that a variety of proteases play important roles in cancer invasion and metastasis. Among these proteases, urokinase-type plasminogen activator (uPA) is particularly important, since its specific binding to the receptor (uPAR) existing on the surface of a cancer cell is considered to be a trigger for cancer invasion. It is thus expected that the blocking of the binding can inhibit cancer invasion in the cancer patients and improve their prognosis dramatically. To develop a potent inhibitor for the binding, many types of peptides of amino acids were produced and their effect on the cancer invasion was investigated in the previous biochemical experiments. On the other hand, our previous ab initio molecular simulations have clarified that some amino acid residues of uPA play important roles in the specific binding between uPA and uPAR. In the present study, we propose some peptides composed of these important residues and investigate the specific interactions and the binding affinity between uPAR and the peptides at an electronic level, using ab initio molecular simulations. Base on the results simulated, we elucidate which peptide can bind more strongly to uPAR and propose a novel potent peptide which can inhibit the binding between uPAR and uPA efficiently. [ABSTRACT FROM AUTHOR]

Amorphous polymers are among the most common materials used in adhesives, and a clear understanding of the effects of molecular scale features on macroscopic responses is necessary to design new, better performing adhesives. While many features have been investigated, including effects of molecular weight, inclusion of filler materials, and some effects of crosslinking, much of the understanding of the adhesive response remains empirical. Specifically, choosing the appropriate combination of polymer properties that optimize the work required to debond is still a challenge and the interplay between mechanical and chemical properties of polymers at interfaces is largely unknown. Here, we perform molecular dynamics simulations on a simple coarse-grained polymer model to directly investigate the role of crosslinking in determining the adhesive response of amorphous polymers at the molecular level. We find that crosslinking has a dramatic effect on the mechanical properties even at relatively low crosslink densities, and that crosslinking alone can be effective for optimizing the adhesive response of amorphous polymer adhesives. We observe a clear transition from cohesive to adhesive failure as the crosslink density is increased which coincides with the optimal toughening in the films. Furthermore, we find that our model captures the key molecular scale deformation mechanisms that control the adhesive response. For low crosslink densities, increased crosslinking improves the adhesive response by inhibiting chain sliding and allowing the structures to achieve large deformations, but as the crosslink density is increased further, the adhesive response is diminished due to reduced overall deformability. Our results provide simple but important insights into how crosslinking in amorphous polymer adhesives can be used to tune the mechanical response and ultimately to optimize adhesive performance for various applications. [ABSTRACT FROM AUTHOR]