LAUSR

We investigate the dynamics of profilin binding, including differences in binding for the loading and recruiting subregions of VASP, the effect of binding site mutations on peptide affinity for profilin, and the effect of actin binding on profilin dynamics. Ensemble molecular dynamics simulations with bootstrapping of MM/PBSA and MM/GBSAderived free energy calculations are used to robustly estimate binding affinities. The essential features of the interaction between profilin and poly-proline peptides is explored through statistical analyses of simulation data. Background Profilin (Pfn1) is an actin-binding protein that is at the heart of regulation of actin dynamics in cells and an important downstream mediator of actin assembly triggered by RhoGTPases. Pfn1 plays a critical role in angiogenesis. Vasodilator-stimulated phosphoprotein (VASP) primarily serves as an actin filament elongation factor. It recruits GActin to the barbed end of a growing filament by binding profilin preferentially as part of an actin-profilin complex. It has several proline-rich subregions that have different functional roles.