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Speaker:Â Dr. Omar Valsson, Assistant Professor of Theoretical 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 effect 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:
- Predicting Biomolecular Binding Kinetics: A Review – A review about obtaining unbinding kinetics from atomistic simulations; it gives an overview of the field even though it is not authored by Dr. Valsson.
- Enhanced Sampling Methods for Molecular Dynamics Simulations – Section 7.2 discusses the methods that Dr. Valsson uses in his research.