10/7 – Wei Jiang, Argonne National Laboratory

Speaker: Wei Jiang

Computational Science Division, Argonne National Laboratory

Title: Calculation of protein-ligand binding affinities: molecular dynamics simulations with sampling enhancement

Abstract: Protein-ligand binding plays a fundamental role in a vast number of biological processes. Calculations of absolute and relative protein-ligand binding affinity are very often complicated by diverse sampling obstacles, including hysteresis, hidden slow degrees of freedom of macromolecules and wetting-dewetting coupled with ligand insertion. In this talk, sampling enhancement techniques based on Hamiltonian exchange and Hamiltonian simulated annealing, which are incorporated into free energy calculations, are described. Applications of sampling enhanced molecular dynamics simulations for several representative ligand binding problems are elucidated. It is demonstrated that these techniques efficiently accelerate samplings along the binding reaction path and convergence of free energy calculations.