On the relation between residue flexibility and local solvent accessibility in proteins

We investigate the relationship between the flexibility, expressed with B‐factor, and the relative solvent accessibility (RSA) in the context of local, with respect to the sequence, neighborhood and related concepts such as residue depth. We observe that the flexibility of a given residue is strongly influenced by the solvent accessibility of the adjacent neighbors. The mean normalized B‐factor of the exposed residues with two buried neighbors is smaller than that of the buried residues with two exposed neighbors. Inclusion of RSA of the neighboring residues (local RSA) significantly increases correlation with the B‐factor. Correlation between the local RSA and B‐factor is shown to be stronger than the correlation that considers local distance‐ or volume‐based residue depth. We also found that the correlation coefficients between B‐factor and RSA for the 20 amino acids, called flexibility‐exposure correlation index, are strongly correlated with the stability scale that characterizes the average contributions of each amino acid to the folding stability. Our results reveal that the predicted RSA could be used to distinguish between the disordered and ordered residues and that the inclusion of local predicted RSA values helps providing a better contrast between these two types of residues. Prediction models developed based on local actual RSA and local predicted RSA show similar or better results in the context of B‐factor and disorder predictions when compared with several existing approaches. We validate our models using three case studies, which show that this work provides useful clues for deciphering the structure–flexibility–function relation. Proteins 2009. © 2009 Wiley‐Liss, Inc.