Department of Chemistry & Biochemistry, Florida State University
"Orthogonal Space Sampling of Hierarchical Free Energy Landscapes"
Proteins randomly fluctuate in their functional environments. Through long-timescale dynamics, energy can be channeled through hierarchical energy landscapes to eventually lead to functional events. To effectively and accurately sample inter-coupled multi-timescale protein motions, based on the orthogonal space sampling scheme, the high-order orthogonal space tempering (HOOST) method was recently developed. The new method allows for energy flow to be selectively accelerated so as to efficiently activate essential degrees of freedom that are unknown a priori and thereby enables robust sampling of long-timescale motions that enslave target consequential events. The HOOST method can be applied for chemical perturbation and geometrical perturbation based free energy sampling; in addition, based on our solvation force energy landscape model, it can enable general "predictive" sampling of protein functional dynamics. Challenging case studies will be presented in this talk.