BMOL Seminar Series: Dr. Omar Valsson

Seminar Details

Speaker: Dr. Omar Valsson, Assistant Professor of Chemistry at University of North Texas

Host: Dr. Oliviero Andreussi, Chemistry & Biochemistry

Title: Unraveling Protein-Protein Dissociation Kinetics via Atomistic Simulations

Abstract: Obtaining the unbinding/dissociation kinetics of protein-ligand and protein-protein complexes is of great fundamental and practical interest. In particular, the unbinding/residence times of ligands from their target proteins (i.e., k_off, the dissociation rate constant) is a vital parameter as it is known that the dissociation kinetics are directly correlated to the efficacy of a drug. Therefore, obtaining the dissociation kinetics from atomistic simulations has been a fundamental task in the molecular modeling field. Here, enhanced sampling methods are needed as the unbinding event is a rare event on the simulation time scale. While considerable effort has been made to obtain the unbinding/residence times in protein-ligand complexes, there have been much more limited applications towards protein-protein dissociation kinetics.

In this talk, I will discuss my group’s research program that is focused towards unraveling protein-protein dissociation kinetics by using atomistic simulations augmented with advanced sampling methods. I will present our results for the unbinding kinetics of intrinsically disordered peptides from their protein partners, and discuss how the protein model (i.e., force field) can affect the results. I will discuss the future perspective of our research program, including investigating how different stabilizing molecules affect the stability and dissociation kinetics of protein-protein complexes. Furthermore, I will discuss future applications for understanding ternary protein complexes’ stability within targeted protein degradation.

Publications Related to Talk:

A review about obtaining unbinding kinetics from atomistic simulations.

• Predicting Biomolecular Binding Kinetics: A Review

An extensive overview of enhanced sampling methods. Section 7.2 discusses the methods that we use in our research.

• Enhanced Sampling Methods for Molecular Dynamics Simulations