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

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 factors 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. The results indicate no differences in the global values like the average packing factor among the three classes of protein homologues, but at local levels there are differences. A comparison of homologous protein triplets show that the average atomic fluctuations at a given temperature mainly 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 homologues. The computer codes developed and used in this work are available at the link https://github.com/Munna-Sarkar/proteins-rigidity-flexibility.git.

Automated summary

This study investigates the rigidity and flexibility of psychrophilic, mesophilic, and thermophilic proteins using packing factors and atomic fluctuations. The results show no differences in global values, but differences at the local level, with the order of atomic fluctuations being P > M > T. The study suggests altering the rigidity of the active site as a potential strategy to engineer tailor-made psychrophilic or thermophilic proteins.