Comparative analysis of rigidity across protein families

TL;DR

This study applies pebble game rigidity analysis to multiple protein structures across six families, revealing sensitivity to structural variations and identifying characteristic patterns of rigidity loss.

Contribution

It provides a systematic comparison of rigidity analysis results across protein families, emphasizing the importance of constraint selection and revealing distinct rigidity transition patterns.

Findings

Mainchain rigidity is sensitive to small structural variations.

Rigidity loss patterns are either sudden or gradual.

Hydrogen bond constraints should be chosen based on specific hypotheses.

Abstract

Rigidity analysis using the "pebble game" has been applied to protein crystal structures to obtain information on protein folding, assembly and t he structure-function relationship. However, previous work using this technique has not made clear how the set of hydrogen-bond constraints included in the rigidity analysis should be chosen, nor how sensitive the results of rigidity analysis are to small structural variations. We present a comparative study in which "pebble game" rigidity analysis is applied to multiple protein crystal structures, for each of six differen t protein families. We find that the mainchain rigidity of a protein structure at a given hydrogen-bond energy cutoff is quite sensitive to small structural variations, and conclude that the hydrogen bond constraints in rigidity analysis should be chosen so as to form and test specific hypotheses about the rigidity o f a particular protein. Our comparative approach highlights two different characteristic patterns ("sudden" or "gradual") for protein rigidity loss as constraints are re moved, in line with recent results on the rigidity transitions of glassy networks.