Characterizing the folding core of the cyclophilin A - cyclosporin A complex II: improving folding core predictions by including mobility

TL;DR

This study enhances the prediction of protein folding cores by combining rigidity analysis and motion simulations, providing a more accurate theoretical approach for CypA and its complex with CsA.

Contribution

It introduces a combined method using rigidity analysis and motion simulations to improve folding core predictions for proteins.

Findings

Combined approach yields more specific folding core predictions.

Rigidity analysis and motion simulations intersect to identify key residues.

Method applicable to unbound and complexed protein forms.

Abstract

Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids which make up the folding core include hydrogen-deuterium exchange and $\Phi$-value analysis and can be expensive and time consuming. As such there is a desire to improve upon existing methods for determining protein folding cores theoretically. Here, we use a combined method of rigidity analysis alongside coarse-grained simulations of protein motion in order to improve folding core predictions for unbound CypA and for the CypA-CsA complex. We find that the most specific prediction of folding cores in CypA and CypA-CsA comes from the intersection of the results of static rigidity analysis, implemented in the FIRST software suite, and simulations of the propensity for flexible motion, using the FRODA tool.