“Toward Multiscale Modeling of the Effects of Small Molecules on Cellular Pathways”

The rational design of small molecules that modulate cellular activity requires the development of quantitative, predictive models for multiple length and timescales: modeling of the physical binding affinity to a biomolecular target, how the action of binding influences the catalytic activity or behavior of the target, and how both on- and off-target effects modulate cellular pathways. In principle, modeling based on sound statistical mechanics and physical interaction potentials should allow for these processes to be described to sufficient accuracy to be useful for small molecule engineering. I describe progress toward this goal, with special attention to the modeling and measurement of physical binding processes and biomolecular conformational dynamics.