TITLE:
A Structural Comparison Approach for Identifying Small Variations in Binding Sites of Homologous Proteins
AUTHORS:
Ivana Uzelac, Thomas Olsson, Leif A. Eriksson, Johan Gottfries
KEYWORDS:
Protein Comparison, Coagulation Factor, Serine Protease, Binding Site, PCA, OPLS-DA
JOURNAL NAME:
Computational Molecular Bioscience,
Vol.5 No.3,
September
30,
2015
ABSTRACT: A method for analyzing the protein site similarity was devised aiming at understanding selectivity of homologous proteins and guiding the design of new drugs. The method is based on calculating Cα distances between selected pocket residues and subsequent analysis by multivariate methods. Five closely related serine proteases, the coagulation factors II, VII, IX, X, and XI, were studied and their pocket similarity was illustrated by PCA clustering. OPLS-DA was then applied to identify the residues responsible for the variation. By combining these two multivariate methods, we could successfully cluster the different proteases according to class and identify the important residues responsible for the observed variation.