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Center for Nonlinear Studies |
Understanding how a protein's sequence and structure influence dynamics remains a fundamental challenge in biophysics with major implications for protein design and therapeutic development. Recently, we have shown that decomposing temperature responses of inter-residue contacts provides useful insight into the functional dynamics of proteins. The details of this Chemically Accurate Contact Response Analysis (ChACRA) method are presented here along with its application to several proteins. We show that ChACRA directly identifies critical interactions controlling the dynamics of an enzyme active site, the activation of a thermosensitive ion channel, and allostery in two additional enzymes. These examples demonstrate the utility of ChACRA's unsupervised machine learning approach for dissecting allostery and the sequence-structure-dynamics relationship at the residue level.
Host: Hau Thi Bich Nguyen (B-TEK)