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

TL;DR

This paper introduces a liquid-theory analogy to direct-coupling analysis in protein sequence alignments, offering new insights into how direct and indirect correlations relate and improving protein structure prediction methods.

Contribution

It presents a novel liquid-theory inspired formulation for direct-coupling analysis, enhancing understanding of correlation origins in protein sequences.

Findings

Direct correlations can be derived using an Ornstein-Zernike-like formulation.

The approach clarifies how indirect correlations emerge from direct ones.

Implications for improved protein contact prediction methods.

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 multiple-sequence 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.