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De novo design provides an attractive approach to test the mechanism by which metalloproteins define the geometry and reactivity of their metal ion cofactors. While there has been considerable progress in designing proteins that bind transition metal ions including iron-sulfur clusters, the design of tetranuclear clusters with oxygen-rich environments has not been accomplished. Here, we describe the design of tetranuclear clusters, consisting of four Zn[sup 2+] and four carboxylate oxygens situated at the vertices of a distorted cube-like structure. The tetra-Zn[sup 2+] clusters are bound at a buried site within a four-helix bundle, with each helix donating a single carboxylate (Glu or Asp) and imidazole (His) ligand, as well as second- and third-shell ligands. Overall, the designed site consists of four Zn[sup 2+] and 16 polar side chains in a fully connected hydrogen-bonded network. The designed proteins have apolar cores at the top and bottom of the bundle, which drive the assembly of the liganding residues near the center of the bundle. The steric bulk of the apolar residues surrounding the binding site was varied to determine how subtle changes in helix -- helix packing affect the binding site. The crystal structures of two of four proteins synthesized were in good agreement with the overall design; both formed a distorted cuboidal site stabilized by flanking second- and third-shell interactions that stabilize the primary ligands. A third structure bound a single Zn[sup 2+] in an unanticipated geometry, and the fourth bound multiple Zn[sup 2+] at multiple sites at partial occupancy. The metal-binding and conformational properties of the helical bundles in solution, probed by circular dichroism spectroscopy, analytical ultracentrifugation, and NMR, were consistent with the crystal structures. [ABSTRACT FROM AUTHOR]

Zwitterioniccarboxybetaine and sulfobetaine materials have shownan excellent ability to resist nonspecific protein adsorption. Itis desirable to obtain a better understanding of zwitterionicmaterials based on their molecular structures. This work aims to understandthe roles of charged groups in zwitterionic moieties and todesign new protein-resistant zwitterionic moieties beyond carboxybetaineand sulfobetaine. We conducted molecular simulations to studythe hydration, self-association, and protein interactions of 12 zwitterionicmoieties derived from three anionic groups (carboxylic, sulfonate,and sulfate) and four cationic groups (quaternary ammonium, tertiaryammonium, secondary ammonium, and primary ammonium). The partial chargesof atoms in these moieties were obtained from quantum chemical calculations.Hydration was studied by evaluating the hydration free energy of moietiesand the hydration structure and dynamics of the charged groups. Allzwitterionic moieties have strong hydration, but their structuraland dynamic properties depend on the types of cationic and anionicgroups involved. The self-association and protein interactions ofzwitterionic moieties also show relationships with the chargedgroups. Our simulation results indicate good protein-resistant abilityof several zwitterionic moieties, one of which has also beenshown by recent experiments. [ABSTRACT FROM AUTHOR]

Zwitterionic materials have showntheir excellent performance inmany biological and chemical applications. Zwitterionic materialspossess moieties that own both cationic and anionic groups. The associationsamong zwitterionic moieties through electrostatic interactions playan important role in properties of zwitterionic materials. However,the relationship between the molecular structures and associationsof zwitterionic moieties are still not well understood. This workcompared thermal- and salt-responsive behaviors of sulfobetaine andcarboxybetaine polymers by examining their rheological propertiesas a function of temperature and their hydrodynamic sizes as a functionof salt concentration. Results showed that carboxybetaine polymersdo not exhibit stimuli responses as expected from the antipolyelectrolytebehavior of zwitterionic polymers as observed in sulfobetaine polymers.We studied and compared the associations among zwitterionic moietiesin these two zwitterionic polymers using molecular dynamic simulations.Simulation results show that the charge-density difference betweencationic and anionic groups determines the associations among zwitterionicmoieties, which are responsible for different stimuli responses ofcarboxybetaine and sulfobetaine polymers. [ABSTRACT FROM AUTHOR]

Zwitterionic carboxybetaines (CBs) are ubiquitous innature andconsidered promising materials for biological and chemical applications.A thorough understanding of the effect of carbon spacer length (CSL)on molecular properties is important. In this work, using moleculardynamics simulation and quantum chemical calculation, we investigatedthe effect of CSL on the molecular properties of CB molecules. Thehydration number, structure, and dynamics of carboxylic and trimethylammonium groups were investigated and found to present different behaviorsin regards to the variation of CSL. The simulation results with partialcharges developed from quantum chemical calculations were comparedwith those with partial charges from the OPLS all atom (OPLSAA) forcefield. The hydration free energy of CB molecules and CB–Na+association was also studied as a function of CSL. [ABSTRACT FROM AUTHOR]

Quantitative analysis of single molecule experimentsshow thatadding either of two natural polyamines, spermine or spermidine, producedmore compact plectonemes in DNA in physiological concentrations ofmonovalent salt. They also promoted plectoneme formation at lowervalues of torsion in measurements of extension versus twist. Quantifyingchanges in the plectonemic DNA using some results from simple rodmodels suggested that exposure to polyamines reduced the radii andincreased the densities of plectonemes. Thus, polyamines may limitthe twist density by favoring writhe which maintains the B-form. Althoughpolymerases may significantly stretch the double helix, denature DNA,and produce twist instead of writhe, natural polyamines stabilizebase-pairing, limit twist to maintain the B-form, and promote supercoiling,which is conducive to replication and transcription and essentialfor DNA packaging. [ABSTRACT FROM AUTHOR]

In this work, molecular dynamics simulations were performed to study a carboxybetaine methacrylate (CBMA) hydrogel under various swelling states. The water content in this study ranged from 28% to 91% of the total weight of the hydrogel. Three transitions of the CBMA hydrogel were observed as the water content increased. The first transition occurs when the water content increases from 33% to 37%. The observed kink in the self-diffusion coefficient of water indicates that the hydration of the polymer network of the hydrogel is saturated; the further added water is in a less confined state. The second transition was found to be related to the physical cross-links of the polymer network. As the water content rises to above 62%, the lifetime of the physical cross-links decreases significantly. This abrupt change in the lifetime indicates that the transition represents the equilibrium swelling state of the hydrogel. Finally, the third transition was observed when the water content goes above 81%. The significant increases in the bond and angle energies of the polymer network indicate that the hydrogel reaches its upper limit swelling state at this transition. These results are comparable to previously published experimental studies of similar zwitterionic hydrogels. [ABSTRACT FROM AUTHOR]

Using molecular dynamics simulations, we investigated the associations between two zwitterions (carboxybetaine and sulfobetaine) and four types of cations (Li, Na, K, and Cs) in aqueous solutions. We studied the number and lifetime of various zwitterion–cation associations and observed that both carboxybetaine and sulfobetaine have the same order of association number and lifetime: Li> Na> K> Cs. Simulation results showed that the association variation as a function of cation types for these two zwitterions is significantly different. The effect of anion type on the order was also investigated by varying the type of anions from Cl–to Br–and F–. In order to further investigate zwitterion–cation association, we simulated the systems either with one type of zwitterion and two types of cations or with one type of cation and both carboxybetaine and sulfobetaine presented. This allowed direct competition between the solutes, and the observed association number and lifetime validated the order. Simulation results further demonstrated that, although CB associates stronger with Li橷 Na똖 SB, the latter is associated preferentially by K橷 Cs. [ABSTRACT FROM AUTHOR]

How the geometry of nanosized confinement affects dynamics of biomaterials is interesting yet poorly understood. An elucidation of structural details upon nanosized confinement may benefit manufacturing pharmaceuticals in biomaterial sciences and medicine. The behavior of biopolymers in nanosized confinement is investigated using coarse-grained models and molecular simulations. Particularly, we address the effects of shapes of a confinement on protein-folding dynamics by measuring folding rates and dissecting structural properties of the transition states in nanosized spheres and ellipsoids. We find that when the form of a confinement resembles the geometrical properties of the transition states, the rates of folding kinetics are most enhanced. This knowledge of shape selectivity in identifying optimal conditions for reactions will have a broad impact in nanotechnology and pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Describes the nonlinear conversion of mechanical energy into chemical energy. Efficiency of molecular machines for energy conversion when operating at higher force levels; Description of a series of elastic protein-based polymers that exhibit inverse temperature transitions of hydrophobic folding and assembly.

Chargedamino acids are the most common on surfaces of proteinsand understanding the interactions between these charged amino acids,salt bridging, is crucial for understanding protein–proteininteractions. Previous simulations have been limited to implicit solventor fixed binding geometry due to the sampling required for convergedfree energies. Using well-tempered metadynamics, we have calculatedsalt bridge free energy surfaces in water and confirmed the resultswith NMR experiments. The simulations give binding free energies,quantitative ranking of salt bridging strength, and insights intothe hydration of the salt bridges. The arginine–aspartate saltbridge was found to be the weakest and arginine-glutamate the strongest,showing that arginine can discriminate between aspartate and glutamate,whereas the salt bridges with lysine are indistinguishable in theirfree energy. The salt bridging hydration is found to be complementaryto salt bridge orientation with arginine having specific orientations. [ABSTRACT FROM AUTHOR]

Electrostatic interactions play an important role insetting theaqueous two-phase separation behaviors of mixtures of oppositely chargedsurfactants. The aqueous mixture of cetyltrimethylammonium bromide(CTAB) and sodium dodecylsulfonate (AS) is actually a five-componentsystem, comprised of CTAB, AS, complex salt (cetyltrimethylammoniumdodecylsulfonate, abbreviated as CTA–), NaBr, and water. In the three-dimensional pyramid phase diagram,the aqueous two-phase region with excess AS or with excess CTAB extendssuccessively from the region very near to the NaBr–H2O line through the CTAB–AS–H2O conventionalmixing plane to the CTA––AS–H2O side plane or to the CTA––CTAB–H2O side plane, respectively. Largeor small molar ratios between the counterions and their correspondingsurfactant ions for oppositely charged surfactants located in theNaBr side or the CTA–side of thepyramid imply strong or weak electrostatic screening. Electrostaticscreening of counterions alters the electrostatic attractions betweenthe oppositely charged head groups or the electrostatic repulsionsbetween the like-charged head groups in excess, and the electrostaticfree energy of aggregation thus affects the aqueous two-phase separationmodes. Composition analysis, rheological property investigation, andTEM images suggest that there are two kinds of aqueous two-phase systems(ATPSs). On the basis of these experimental results and Kaler’scell model, two kinds of phase separation modes were proposed. Experimentalresults also indicate that all of the top phases are surfactant-rich,and all of the bottom phases are surfactant-poor; the density differencebetween the top phase and the bottom phase in one ATPS is very small;the interfacial tension (σ) of the ATPS is ultralow. [ABSTRACT FROM AUTHOR]