Insights on Rigidity and flexibility at the Global and Local Levels of Protein Structures and their Roles in Homologous Psychrophilic, Mesophilic and Thermophilic Proteins: A Computational Study

TL;DR

This study investigates the differences in rigidity and flexibility of homologous proteins from psychrophilic, mesophilic, and thermophilic organisms at global and local levels, revealing local variations and potential strategies for protein engineering.

Contribution

It introduces a validated method for comparing atomic fluctuations across proteins by correcting B-factors and normalizing temperature, and highlights local differences in protein flexibility related to thermal adaptation.

Findings

No difference in global packing factors among the three protein classes.

Local atomic fluctuations follow the order P>M>T at the same temperature.

Packing factors and atomic fluctuations are anti-correlated.

Abstract

The rigidity and flexibility of homologous psychrophilic(P), mesophilic(M) and thermophilic(T) proteins have been investigated at the global and local levels in terms of packing factor and atomic fluctuations obtained from B-factors. For comparison of atomic fluctuations, correction of errors by considering errors in B-factors from all sources in a consolidated manner and conversion of the fluctuations to the same temperature have been suggested and validated. Results indicate no differences in the global values like average packing factor among the three classes of protein homologs but at local levels there are differences. Comparison of homologous proteins triplets show that the average atomic fluctuations at a given temperature obey the order P>M>T. Packing factors and the atomic fluctuations are anti-correlated suggesting that altering the rigidity of the active site might be a potential strategy to make tailor made psychrophilic or thermophilic proteins from their mesophilic homologs.