Cosurim: A program for automated computation of composition of core, rim and surface of protein data bank files and its applications

摘要

Primary structure of protein is composed of polar and non-polar amino acids, whose distributions pattern along the sequence is not well understood. However, when this extended form of the sequence is kept in aqueous solution, the non-polar constituents form the compact hydrophobic core, keeping the polar residues in the contact of bulk water in the surface of the protein that eventually takes a globular shape. This hydrophobic collapse is an entropy driven and spontaneous process. While residues in the surface are stabilized by hydrogen bonding with bulk water, the core residues are largely stabilized by Van der Waals interactions. It seems, the process of compact core formation is apparently not unique in that the core of the protein may contain isolated charged and or polar side chains and the surface may harbour hydrophobic patches. Further, between the core and the surface, there may exist a rim region, whose composition is yet to be verified. The fact that manual determination of compositions involving a large dataset of x-ray structures would be highly labour intensive, time consuming and error prone, automation in these aspects would be very useful. In this end, our software, Cosurim (available at https://sourceforge.net/projects/cosurim/) is capable of determination of composition in core-surface or core-rim-surface format, for any number of protein structures with any number of chains in them. Analyses involving orthologous proteins that are adapted under diverse environmental conditions show that although core has strong preference for bulky hydrophobic residues, polar and charged residues are also present. Same is true for surface region. Interestingly, analysis of RNase H1 using core-rim-surface mode of the program show the rim has the lowest content of all classes, indicated discontinuity between the core and the surface. Taken together, Cosurim is a fully automated program for analysis of a single or a database of protein structures for absolute and normalized compositions of core, rim and surface and find applications in structural biology and bioinformatics.