2024 Weston and Sheila Borden Endowed Lecture in Theoretical Chemistry
Channel: UW Chemistry
Date: 2024-02-29

"Overcoming the Multiscale Challenge for Biomolecular Systems"
Professor Gregory A. Voth – Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago
Host: Anne McCoy

Advances in theoretical and computational methodology will be presented along with certain key applications. These advances have been developed over the past 20 years to study complex biomolecular and other soft matter systems across multiple length and time scales via multiscale computer simulation. Our approach provides a systematic connection between all-atom molecular dynamics, coarse-grained (CG) modeling, and mesoscopic phenomena. At the heart of these concepts are “bottom-up” CG methods for deriving such models from molecular structures and their underlying atomic-scale interactions. An important evolving 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 particles 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 of the underlying molecules, while still maintaining a high degree of resolution reduction and simplification in the CG modeling. The presence of the UCG site internal states greatly expands the possible range of systems amenable to accurate CG modeling, i.e., heterogeneous systems, including complex self-assembly and aggregation processes involving many proteins. The original development of this “multiscale coarse-graining” approach involved aspects of machine learning although it was not referred to as such at the time. Our approach has of course evolved to the current day and machine learning has become a key tool. A significant pay-off application from this multi-year effort has focused on biomolecular active matter such as cytoskeleton filaments (e.g., actin), while another important set of problems has involved processes in virus replication and especially the assembly of the HIV-1 virus capsid from over one thousand protein – a phenomenon involving a billion or more atoms over long timescales that cannot be approached through all-atom MD simulation.

This lecture is supported by the Weston and Sheila Borden Endowed Fund in Chemistry, established by the Bordens in 2015. Weston T. Borden served on the University of Washington chemistry faculty for 31 years. His research involved the use of molecular orbital (MO) theory and MO-based calculations to understand and predict the structures and reactions of organic and organometallic molecules. Sheila Borden received her B.Sc. and Ph.D. degrees in chemistry from the University of Newcastle upon Tyne. After a year at the University of Oslo, she joined the staff of the Royal Society of Chemistry, where she eventually became managing editor of the RSC's organic chemistry journals. In 2004, she moved to the University of North Texas to lead the JACS Editorial Office.