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

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.