Speaker: Dr. Mahmoud Moradi, University of Arkansas | Department of Chemistry and Biochemistry
Date: Friday, September 30, 2022, 2:00 – 3:00 PM
Location: Science Engineering Hall (SCEN 204)
Title: Computational Exploration of Protein Conformational Space
Abstract: With recent advances in various biophysical techniques, structural biology is at a tipping point. However, there seems to be an effective uncertainty relation between the spatial and temporal resolution of these techniques; the spatially high-resolution techniques such as x-ray crystallography are lacking a temporal resolution and the temporally high-resolution techniques such as single-molecule FRET spectroscopy are associated with very low spatial resolutions. Currently, a detailed picture of protein dynamics at the atomic level with a high spatiotemporal resolution can be produced only using all-atom molecular dynamics (MD) simulations. Unfortunately, many biomolecular processes such as large-scale protein conformational changes are associated with timescales inaccessible to brute-force MD. Although various enhanced sampling techniques have been developed over the past few decades to address this “timescale gap”, the application of these methods to biologically relevant systems remains challenging. We have recently developed a Riemannian framework for improving the theoretical foundations of enhanced sampling techniques for the computational study of conformational transitions of proteins. This formalism provides a robust framework for the study of functionally important conformational changes of proteins at the molecular level. The developed algorithms have been particularly used to study several classes of proteins including but not limited to membrane insertases, chloroplast signal recognition particles, fibroblast growth factor proteins, mechanosensitive channels, influenza hemagglutinin, and coronavirus spike proteins.
Bio: Mahmoud Moradi is an associate professor of chemistry and biochemistry at the University of Arkansas, Fayetteville. He received his B.Sc. and M.Sc. in physics from Sharif University of Technology in Iran. He received a PhD in physics from NC State University in 2011. His postdoctoral work at the Beckman Institute, University of Illinois at Urbana-Champaign focused on developing and applying free energy calculation methods to study membrane transporters. He joined the faculty at the Department of Chemistry and Biochemistry, University of Arkansas in 2015. His research is centered around two inter-related questions: (i) how do proteins function by changing their conformation and undergoing concerted motions? and (ii) how can we simulate these functionally important conformational changes at an atomic level? His lab is developing theories and methodologies and applying these methods to study conformational dynamics and free energy landscapes of proteins from fibroblast growth factor to influenza hemagglutinin and coronavirus spike protein. He is the recipient of the NIH outstanding investigator (R35) award and the NSF CAREER award.
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