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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]

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]

To investigate the consequences of macromolecular crowding on the behavior of a globular protein, we performed a combined experimental and computational study on the 148-residue single- domain α/β protein, Desulfovibrio desulfuricans apoflavodoxin. In vitro thermal unfolding experiments, as well as assessment of native and denatured structures, were probed by using far-UV CD in the presence of various amounts of Ficoll 70, an inert spherical crowding agent. Ficoll 70 has a concentration-dependent effect on the thermal stability of apoflavodoxin (ΔTm of 20°C at 400 mg/ml; pH 7). As judged by CD, addition of Ficoll 70 causes an increase in the amount of secondary structure in the native-state ensemble (pH 7, 20°C) but only minor effects on the denatured state. Theoretical calculations, based on an off-lattice model and hardsphere particles, are in good agreement with the in vitro data. The simulations demonstrate that, in the presence of 25% volume occupancy of spheres, native flavodoxin is thermally stabilized, and the free energy landscape shifts to favor more compact structures in both native and denatured states. The difference contact map reveals that the native-state compaction originates in stronger interactions between the helices and the central β-sheet, as well as by less fraying in the terminal helices. This study demonstrates that macromolecular crowding has structural effects on the folded ensemble of polypeptides. [ABSTRACT FROM AUTHOR]

Abstract: The behaviors of the ionic hydration in nanopore are of both biological and chemical interests. Using carbon nanotube (CNT) as the 1-D nanopore model, we investigated the effect of the modified groups (Cing on the pore inner wall on the hydration of Li+, Na+ and K+ with molecular dynamics simulation. The structures of the water molecules around the cations confined in the modified CNTs were compared with their counterparts in the pristine CNTs. Among the three cations, the sequence of the sensitivity for the spatial and orientation distributions of the water molecules in the first coordination shells is: K+ >Na+ >Li+. The same modification results in the opposite effects for the ionic hydration inside the (10, 10) and (8, 8) CNTs. Inside the (10, 10) CNT, the modification enhances the ionic hydration, whereas inside the (8, 8) CNT, the ionic hydration is weakened by the modification of CNT wall. [ABSTRACT FROM AUTHOR]

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]