Abstract

The design of airplanes, bridges, chemical plants, and computer chips is aided significantly by modern computational tools. Design of novel molecules, however, is done primarily by trial-and-error. A  prime example is the pharmaceutical industry, where the complexity of biomolecular interactions has  greatly limited our ability to model and design effective small molecule drugs. This means drug design has  remained somewhat of a black art, relying on many ad hoc assumptions and on the intuitive insights of  experienced medicinal chemists. What are the barriers that must be overcome in order to model drug ligand binding affinities, solubilities, partitioning into delivery formulations and polymorph stabilities  effectively? Is there a hope to change the process of designing drugs with high efficacy, good bioavailability and a specific mode of action from a trial-and-error art to a nanoscale engineering process  using high-quality, reliable modeling?

In my talk, I will discuss the barriers above, some of the successes that are emerging in the field, and  describe research in the Shirts group on modeling the noncovalent interactions of small molecules with  sufficient reliability and efficiency to have a place in the modern pharmaceutical workflow. In particular, I  will discuss approaches we are developing to predict binding affinities of small molecules to proteins,  predict the stability of different polymorphs of solid forms of these small molecule drugs, and develop  sufficiently quantitative force fields for these molecules. 

Biography

This installment of the CBE Fall 2020 Lecture Series will feature Michael Shirts, associate professor of chemical and biological engineering at the University of Colorado Boulder.

Dr. Michael Shirts is an associate professor of Chemical and Biological Engineering at the University  of Colorado Boulder. He received his Ph.D. in Chemistry from Stanford University, and was a NIH NRSA  Ruth L. Kirschstein postdoctoral fellow at Columbia. He has won a number of awards, including the NSF  

CAREER Award, the ACS Computers in Chemistry Junior Faculty Award, and the AICHE CoMSEF Impact  Award in 2020. He is adjusting to working in his bedroom since his kindergartner has commandeered the home office for remote schooling this semester.

Zoom webinar sponsored by the Department of Chemical and Biomolecular Engineering