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We describe the development of the AMBER force field parameters for 46 nucleases involving most kinds of copper nucleases with high DNA affinities and specificities by MINA approach that could evaluate accurate force constants for batch bonds/angles on the basis of energies of three adjacent lengths/angles geometries. The molecular mechanics (MM) and molecular dynamic simulations on adducts of the 21 representative copper-based nucleases with DNA are in excellent agreement with those of experimental results. Furthermore, to validate the evaluated parameters, the studied structures performed frequency analysis together with normal mode calculations in quantum mechanics and MM calculations. The force field parameters evaluated in this work provide an extension of AMBER force field, and the results of molecular dynamics simulations of adduct of copper nuclease and duplex DNA illustrate the potential utility of these parameters. [ABSTRACT FROM AUTHOR]

In the present work, molecular simulations were performed for the purpose of predicting the binding modes of four types of copper nucleases (a total 33 compounds) with DNA. Our docking results accurately predicted the groove binding and electrostatic interaction for some copper nucleases with B-DNA. The intercalation modes were also reproduced by “gap DNA”. The obtained results demonstrated that the ligand size, length, functional groups and chelate ring size bound to the copper center could influence the binding affinities of copper nucleases. The binding affinities obtained from the docking calculations herein also replicated results found using MM-PBSA approach. The predicted DNA binding modes of copper nucleases with DNA will ultimately help us to better understand the interaction of copper compounds with DNA. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations of crystals can enlighten interpretation of experimental X-ray crystallography data and elucidate structural dynamics and heterogeneity in biomolecular crystals. Furthermore, because of the direct comparison against experimental data, they can inform assessment of molecular dynamics methods and force fields. We present microsecond scale results for triclinic hen egg-white lysozyme in a supercell consisting of 12 independent unit cells using four contemporary force fields (Amber ff99SB, ff14ipq, ff14SB, and CHARMM 36) in crystalline and solvated states (for ff14SB only). We find the crystal simulations consistent across multiple runs of the same force field and robust to various solvent equilibration schemes. However, convergence is slow compared with solvent simulations. All the tested force fields reproduce experimental structural and dynamic properties well, but Amber ff14SB maintains structure and reproduces fluctuations closest to the experimental model: its average backbone structure differs from the deposited structure by 0.37Å ; by contrast, the average backbone structure in solution differs from the deposited by 0.65Å . All the simulations are affected by a small progressive deterioration of the crystal lattice, presumably due to imperfect modeling of hydrogen bonding and other crystal contact interactions; this artifact is smallest in ff14SB, with average lattice positions deviating by 0.20Å from ideal. Side-chain disorder is surprisingly low with fewer than 30% of the nonglycine or alanine residues exhibiting significantly populated alternate rotamers. Our results provide helpful insight into the methodology of biomolecular crystal simulations and indicate directions for future work to obtain more accurate energy models for molecular dynamics. [ABSTRACT FROM AUTHOR]

Background Molecular dynamics simulations can complement experimental measures of structure and dynamics of biomolecules. The quality of such simulations can be tested by comparisons to models refined against experimental crystallographic data. Methods We report simulations of DNA and RNA duplexes in their crystalline environment. The calculations mimic the conditions for PDB entries 1D23 [d(CGATCGATCG)2] and 1RNA [(UUAUAUAUAUAUAA)2], and contain 8 unit cells, each with 4 copies of the Watson–Crick duplex; this yields in aggregate 64 μs of duplex sampling for DNA and 16 μs for RNA. Results The duplex structures conform much more closely to the average structure seen in the crystal than do structures extracted from a solution simulation with the same force field. Sequence-dependent variations in helical parameters, and in groove widths, are largely maintained in the crystal structure, but are smoothed out in solution. However, the integrity of the crystal lattice is slowly degraded in both simulations, with the result that the interfaces between chains become heterogeneous. This problem is more severe for the DNA crystal, which has fewer inter-chain hydrogen bond contacts than does the RNA crystal. Conclusions Crystal simulations using current force fields reproduce many features of observed crystal structures, but suffer from a gradual degradation of the integrity of the crystal lattice. General significance The results offer insights into force-field simulations that test their ability to preserve weak interactions between chains, which will be of importance also in non-crystalline applications that involve binding and recognition. This article is part of a Special Issue entitled Recent developments of molecular dynamics. [ABSTRACT FROM AUTHOR]

Highlights: [•] Inclusions for heterocyclic peptide (HCD) with isomers are studied by MD. [•] The results indicated that HCD could differentiate the MPP and NPA isomer. [•] The current work hints HCD as a desirable host for molecular recognition. [ABSTRACT FROM AUTHOR]

In the present study, molecular dynamic simulations havebeen performed to investigate the DNA binding affinities and cleavageactivities of a new class of mononuclear copper (p-Cu(BPA) and m-Cu(BPA)) and dinuclear copper–platinum(p-Cu(BPA)-Pt and m-Cu(BPA)-Pt)metallonucleases. The simulated results reveal that the two mononuclearnucleases are noncovalent minor groove DNA binders and the two dinuclearones tend to be bound to DNA in the major groove by a covalent bondbetween the platinum center and N7 of the guanine base, which is inagreement with the experimental results. The simulated results showthat the binding affinities of the four studied nucleases with DNAare in the order of p-Cu(BPA) < m-Cu(BPA) < p-Cu(BPA)-Pt < m-Cu(BPA)-Pt; the binding affinities are dominated by intermolecularbinding modes of nucleases with DNA and the intermolecular hydrogenbonds. The distance probability distributions indicate that the hydrogenatoms of DNA sugar could be abstracted by the four nucleases. Specifically,the dinuclear nucleases abstract hydrogen atoms from the deoxyribosesugar linking to G18base while mononuclear nuclease abstractshydrogen atoms from the deoxyribose sugars linking to C15and C16bases, suggesting that the dinuclear nucleasesimprove the sequence-selective cleavage of DNA compared with the mononuclearone. Moreover, the differences in calculated DNA conformational dynamicsand groove parameters demonstrate that the extent of DNA conformationaldistortions induced by dinuclear nucleases is greater than that inducedby mononuclear nucleases. This investigation provides detailed informationshowing that dinuclear nucleases have superior DNA binding affinitiesand nuclease activities as compared with their mononuclear counterparts. [ABSTRACT FROM AUTHOR]

Although ZnSe has been widely studied due to its attractive electronic and optoelectronic properties, limited data on its plastic deformations are available. Through molecular dynamics simulations, we have investigated the indentations on the (001), (110), and (111) planes of ZnSe nano films. Our results indicate that the elastic modulus, incipient plasticity, elastic recovery ratio, and the structural evolutions during the indenting process of ZnSe nano films show obvious anisotropy. To analyze the correlation of structural evolution and mechanical responses, the atomic displacement vectors, atomic arrangements, and the dislocations of the indented samples are analyzed. Our simulations revealed that the plastic deformations of the indented ZnSe nano films are dominated by the nucleation and propagation of 1/2<110> type dislocations, and the symmetrically distributed prismatic loops emitted during the indenting process are closely related with the mechanical properties. By studying the evolutions of microstructures, the formation process of the dislocations, as well as the formation mechanisms of the emitted prismatic loops under the indented crystalline planes are discussed. The results presented in this work not only provide an answer for the questions about indentation responses of ZnSe nano films, but also offer insight into its plastic deformation mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Although the recently synthesized nanotwinned diamond was found with Vickers hardness exceeding 200 GPa, almost twice the commonly quoted hardness of single crystal diamond, there are still some controversies about the twin-size effects on its hardness and the related plastic deformation mechanisms under Vickers indentations. Through molecular dynamics simulations, we have investigated the behaviors of nanotwinned diamond models under Vickers indentations. Our results indicate that the hardness of nanotwinned diamond would increase with the decreasing of twin boundary separations, but the increasing rate would be reduced due to the concentrated twin boundaries. A formula was given to depict the relationship between hardness and twin thickness, and was consistence with the simulation results. We found that the hardness of nanotwinned diamond is mainly resulted from the competition between strengthening and softening effects of twin boundaries, and the related mechanisms are qualitatively discussed. This work not only provide an answer for the questions about the hardness of nanotwinned diamond versus twin boundary separations, but also offer insights into the plasticity of nanotwinned diamond, which could be beneficial to the design of novel nano structured ultrahard materials and evaluate their origins of hardness and strength. [ABSTRACT FROM AUTHOR]

Although nanostructuring strategies can greatly enhance the hardness of diamond, a large amount of grain boundaries were involved, and little research has been reported on the effect of grain boundaries on the indentation hardness and plastic deformation of diamond. Through molecular dynamics simulations, we have systematically investigated the diamond symmetrical 〈001〉 tilt grain boundaries under Vickers indentations. Our results indicate that the smaller the misorientation angle is, the more favorable for the hardness enhancement of diamond. For the symmetrical 〈001〉 tilt grain boundaries models with misorientation angles smaller than 36.87°, the plastic deformations are mainly resulted from the dislocation propagation mode. For the grain boundaries with misorientation angles larger than 36.87°, the plastic deformation is mainly through the atomic disordering mode, accompanied with the dislocation mode. The effects of grain boundaries on dislocation activities and atomic disordering transformations are systematically discussed. The results presented in this work not only answered the question about the effect of symmetrical 〈001〉 tilt grain boundaries on the hardness of diamond, but also offers fundamental insights for understanding the indentation induced plastic deformation mechanisms of diamond grain boundaries, which could provide reference data for the design of novel nano structured superhard materials. [Display omitted] • The hardness of ∑41(190) grain boundary model is higher than that of (001) plane of diamond. • Increasing of misorientation angle is unfavorable for the hardness improvement of polycrystalline diamond. • Dislocations activities and atomic disordering transformations are two modes of plastic deformations. • Increasing misorientation angle weakens the inhibition of grain boundary on dislocation and atomic disordering activities. [ABSTRACT FROM AUTHOR]