Overcoming the Multiscale Simulation Challenge for Biomolecular Systems
Gregory A. Voth
Department of Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA
Advances in theoretical and computational methodology will be presented that are designed to simulate complex (biomolecular and other soft matter) systems across multiple length and time scales. The approach provides a systematic connection between all-atom molecular dynamics, coarse-grained modeling, and mesoscopic phenomena. At the heart of these concepts are methods for deriving coarse-grained (CG) models from molecular structures and their underlying atomic-scale interactions. This particular aspect of the work has strong connections to the procedure of renormalization in physics, but in the context of CG models it is developed and implemented for more heterogeneous systems. An important new component of our work has also been the concept of the “ultra-coarse-grained” (UCG) model and its associated computational implementation. In the UCG approach, the CG sites or “beads” can have internal states, much like quantum mechanical states. These internal states help to self-consistently quantify a more complicated set of possible interactions within and between the CG sites, while still maintaining a high degree of coarse-graining in the modeling. The presence of the UCG site internal states greatly expands the possible range of systems amenable to accurate CG modeling, i.e., quite heterogeneous systems, including complex self-assembly processes involving large multi-protein complexes. Applications to experimentally important targets such as cytoskeleton actin filaments and HIV virions will be given.