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

Abstract

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.

On the Relationship Between Residue Solvent Exposure and Thermal Fluctuations in Proteins

“…In a dataset comprising 972 non-homologous protein sequences, 86% of the proteins have a correlation coefficient between z B and z sRSA larger than 0.5. The results are consistent with the research by previous work (Zhang et al, 2009) showing the linear relationship between RSA and B-value profiles. In addition, we show that the relationship is not equal for residues in the environments of different rigidity.…”

“…Residue flexibility was known to be correlated to its ASA in single protein (Sheriff et al, 1985) or small dataset (Carugo & Argos, 1997). In a related study, the impact of the ASA of immediate and further neighbors of investigated residues was also noted (Zhang et al, 2009). In this study, we further discuss the relationship between ASA and theoretical thermal fluctuations which are not reported in previous studies.…”

“…The relationships between thermal fluctuation and some concepts related to ASA have been studied. B-factor has shown to correlate to local packing densities (Halle, 2002), atomic distance to protein center-of-mass (Shih et al, 2007;Lu et al, 2008) and residue depth (Zhang et al, 2009). Residue flexibility was known to be correlated to its ASA in single protein (Sheriff et al, 1985) or small dataset (Carugo & Argos, 1997).…”

A Mechanism for Localized Dynamics-driven Affinity Regulation of the Binding of von Willebrand Factor to Platelet Glycoprotein Ibα

“…As a result, the local mobility of A1 increases (Fig. 4B) (58). The phenomenon of water molecules participating in the intramolecular interaction of A1 was observed with the x-ray crystallography (23).…”

<i>In-silico</i> Rational Protein Engineering and Design Approach to Improve Thermostability of a Haloalkane Dehalogenase Enzyme

“…So along with the surface exposed hydrophilic residues and core hydrophobic residues, the surface hydrophobic residues in the loop region also play a significant role in attaining thermo stability (Zhang et al, 2009;Moret and Zebende, 2007). This factor can be considered as a new protein design strategy for this particular enzyme to achieve thermo stability.…”