2008 Annual Meeting
(5ce) Multiscale Biophysics: Theory and Application to the Dynamics of Actin and Actin-Related Structures
Author
The structure, properties and function of the cytoskeleton are determined in large part by the matrix of actin filaments, fibers and bundles that constitute the makeup of cytoskeletal architecture. Recently it has been determined that the directed assembly and growth of the network of actin filaments are responsible for cell motility. A key component of this network is the Arp2/3 complex, whose major function is to serve both as a nucleation site for new actin filaments and as an anchor/branch point between existing filaments. We have performed molecular dynamics (MD) simulations of the isolated Arp2/3 complex and probed the interaction between Arp2/3 and full actin filaments. In turn, results obtained from these simulations have been translated into coarse-grained (CG) models that are able to propagate atomic-level details to meso- and larger length scales.
The second part of this poster presents an investigation of the folding of an important alpha-helical domain within the G-actin protein. Such computational investigations present unique challenges given that many protein folding events occur on far longer timescales than those accessible by traditional molecular simulations. Transformation between the folded and unfolded states requires the crossing of a free-energy barrier that is much larger than kBT, and therefore extremely unlikely to be observed during a classical MD simulation. To address these challenges, we have used the method of metadynamics, which is able to bias a simulation along a set of collective variables that offer a reduced description of the process of interest. Using metadynamics allows one to faithfully reconstruct the free-energy surface for the folding event, and to obtain, among other things, estimates of the free-energy differences between the folded and unfolded state as well as an estimate of the free-energy barrier for folding.