No abstract

A general method has been developed to characterize the hydrophobicity or hydrophilicity of the microenvironment (MENV), in which a given amino acid side chain is immersed, by calculating a quantitative property descriptor (QPD) based on the relative (to water) hydrophobicity of the MENV. Values of the QPD were calculated for a test set of 733 proteins to analyze the modulating effects on amino acid residue properties by the MENV in which they are imbedded. The QPD values and solvent accessibility were used to derive a partitioning of residues based on the MENV hydrophobicities. From this partitioning, a new hydrophobicity scale was developed, entirely in the context of protein structure, where amino acid residues are immersed in one or more "MENVpockets." Thus, the partitioning is based on the residues "sampling" a large number of "solvents" (MENVs) that represent a very large range of hydrophobicity values. It was found that the hydrophobicity of around 80% of amino acid side chains and their MENV are complementary to each other, but for about 20%, the MENV and their imbedded residue can be considered as mismatched. Many of these mismatches could be rationalized in terms of the structural stability of the protein and/or the involvement of the imbedded residue in function. The analysis also indicated a remarkable conservation of local environments around highly conserved active site residues that have similar functions across protein families, but where members have relatively low sequence homology. Thus, quantitative evaluation of this QPD is suggested, here, as a tool for structure-function prediction, analysis, and parameter development for the calculation of properties in proteins.

In this work, we present the wetting property of the edges of a monatomic step on graphite. We have used frictional force microscope to experimentally investigate the wetting property of these edges. We have carried out quantum chemical calculations on a model system of nanographene to characterize hydrogen-bonding interactions between water and two different edges of the graphene, namely, the zigzag and arm-chair edges, to explain our experimental results. We have clearly observed two distinct frictional properties along the monatomic steps on graphite surface under varying conditions of humidity. The distinct frictional properties of the edges have been attributed to the different wetting properties associated with two different edges. Our subsequent quantum chemical calculations complement experimental findings with edge-specific graphene–water interaction.

We have demonstrated earlier that protein microenvironments were conserved around disulfide-bridged cystine motifs with similar functions, irrespective of diversity in protein sequences. Here, cysteine thiol modifications were characterized based on protein microenvironments, secondary structures and specific protein functions. Protein microenvironment around an amino acid was defined as the summation of hydrophobic contributions from the surrounding protein fragments and the solvent molecules present within its first contact shell. Cysteine functions (modifications) were grouped into enzymatic and non-enzymatic classes. Modifications studied were-disulfide formation, thio-ether formation, metal-binding, nitrosylation, acylation, selenylation, glutathionylation, sulfenylation, and ribosylation. 1079 enzymatic proteins were reported from high-resolution crystal structures. Protein microenvironments around cysteine thiol, derived from above crystal structures, were clustered into 3 groups-buried-hydrophobic, intermediate and exposed-hydrophilic clusters. Characterization of cysteine functions were statistically meaningful for 4 modifications (disulfide formation, thioether formation, sulfenylation, and iron/zinc binding) those have sufficient amount of data in the current dataset. Results showed that protein microenvironment, secondary structure and protein functions were conserved for enzymatic cysteine functions, in contrast to the same function from non-enzymatic cysteines. Disulfide forming enzymatic cysteines were tightly packed within intermediate protein microenvironment cluster, have alpha-helical conformation and mostly belonged to CxxC motif of electron transport proteins. Disulfide forming non-enzymatic cysteines did not belong to conserved motif and have variable secondary structures. Similarly, enzymatic thioether forming cysteines have conserved microenvironment compared to non-enzymatic cystienes. Based on the compatibility between protein microenvironment and cysteine modifications, more efficient drug molecules could be designed against cysteine-related diseases.