Liquid-theory analogy of direct-coupling analysis of multiple-sequence alignment and its implications for protein structure prediction

Abstract

The direct-coupling analysis is a powerful method for protein contact prediction, and enables us to extract “direct” correlations between distant sites that are latent in “indirect” correlations observed in a protein multiplesequence alignment. I show that the direct correlation can be obtained by using a formulation analogous to the Ornstein-Zernike integral equation in liquid theory. This formulation intuitively illustrates how the indirect or apparent correlation arises from an infinite series of direct correlations, and provides interesting insights into protein structure prediction.