Hydration Behavior along the Folding Pathways of Trpzip4, Trpzip5 and Trpzip6

The microscopic properties of water confined within different segments of Trpzip4 (TZ4), Trpzip5 (TZ5), and Trzpip6 (TZ6) have been compared for all the states characterized along their folding pathways. In particular, structural ordering, energetics, and dynamics of water have been examined as the peptide unfolds along the free energy landscape. It is observed that the structuring of tetrahedral network as well as translational and rotational motions of hydration waters confined within the strands and the turn regions are very different, revealing motional heterogeneity in small 16-residue trpzips. The polar and charged groups present at the peptide surface anchor to water molecules through hydrogen bonds and are responsible for differential hydration among various segments of the peptide, which is found to be correlated to their hydropathy values. The coherent collective dynamics of water is strongly coupled with conformational changes in the peptide since the trends observed in most of the computed quantities are in accordance with the folded and unfolded states classified along the folding pathway for all trpzips. The hydration behavior conform to the heterogeneity observed in the free energy landscape of stable TZ4 with four unfolded states as compared to more flexible TZ5 and TZ6 with two unfolded states each, in addition to the folded state. The hydration waters are observed to regulate the protein dynamics by continuous fluctuations in hydrogen bond network involving lateral side chains that inject conformational motions in the peptide to facilitate its unfolding. The implications of mutations on various aspects of hydration water dynamics including their impact on structural and dynamic organization of hydrogen bonds are also highlighted. Our studies affirm that topology of the free energy landscape is shaped by both spatial organization and dynamic transitions in hydration waters in addition to the conformational fluctuations in the peptide along the folding pathway

Understanding the Nature of Amino Acid Interactions with Pd(111) or Pd–Au Bimetallic Catalysts in the Aqueous Phase

The interaction of methionine (Met) with different bimetallic-segregated surfaces comprising a uniform distribution of strips and islands of Au on the Pd(111) surface was examined using molecular dynamics (MD) simulations. Out of all the segregated and uniformly doped surfaces studied, the design of Pd–Au islands showed some reduction in the interaction energy (<i>E</i>_int = −43.7 kJ/mol) as compared to that of the pure Pd(111) surface (<i>E</i>_int = −50 kJ/mol) for a single Met molecule. However, at a higher coverage of 9 Met molecules/simulation cell, none of the Pd–Au alloy surfaces showed any improvement as compared to the Pd(111) surface. In order to develop a comprehensive understanding of the nature of the nonbonded interaction of aqueous biogenic impurities with the Pd catalyst surface, the MD study was extended to include a variety of aliphatic, S-containing, aromatic, and polar amino acids. The potential of mean force (PMF) profiles were observed to be distinct for each class of amino acids with substantial differences among amino acids with acidic and basic side chains. The side chains of all the polar and aromatic amino acids showed direct contact with the surface while aliphatic amino acids had their hydrophobic side chain aligned away from the surface. Interestingly, lysine (Lys) and tyrosine (Tyr) were the only two amino acids which interacted preferentially via the distant backbone nitrogen and backbone oxygen, respectively, despite their side chains being in direct contact with the metal surface. The strength of interaction was correlated with the size of the amino acid; the interaction energies were observed to be the maximum for large molecules such as arginine (Arg, <i>E</i>_int = −87.7 kJ/mol) and tryptophan (Trp, <i>E</i>_int = −73.4 kJ/mol), while it was a minimum for aliphatic amino acids such as alanine (Ala, <i>E</i>_int = −10.9 kJ/mol). The study is focused on examining the sensitivity of the choice of the preferential interaction site, conformational preferences, and interaction energies to the side-chain specificity