Assistant Professor of Biochemistry & Molecular Biology
Dr. Vilseck's research has sought to improve the predictive accuracy and efficiency of alchemical free energy methodologies to more reliably guide structure-based drug design. He received his Ph.D. in Physical Organic Chemistry in 2016 from Yale University under the direction of William L. Jorgensen, where he employed free energy perturbation theory to investigate small molecule solvation and protein-ligand binding thermodynamics. Dr. Vilseck then received post-doctoral training in Biophysics at the University of Michigan under Charles L. Brooks III. While working in the Brooks lab, Dr. Vilseck assisted with the development of multisite lambda dynamics, an innovative free energy methodology, and demonstrated its utility to guide lead optimization and drug discovery. He joined the faculty within the Department of Biochemistry and Molecular Biology and the Center for Computational Biology and Bioinformatics at Indiana University School of Medicine in 2019. His research group will (i) continue to develop lambda dynamics-based computational techniques, (ii) apply these techniques to in silico structure-based drug design, and (iii) investigate aberrant protein side chain mutations in proliferative and infectious diseases to address on-going drug resistance.
1. Vilseck, J. Z.; Sohail, N.; Hayes, R. L.; Brooks, C. L., III Overcoming Challenging Substituent Perturbations with Multisite λ-Dynamics: A Case Study Targeting β-Secretase 1. J. Phys. Chem. Lett. 2019, 10, 4875-4880.
2. Vilseck, J. Z.; Armacost, K. A.; Hayes, R. L.; Goh, G. B.; Brooks, C. L. III Predicting Binding Free Energies in a Large Combinatorial Chemical Space Using Multisite λ Dynamics. J. Phys. Chem. Lett. 2018, 9, 3328-3332.
The Vilseck Laboratory is focused on the development and application of state-of-the-art computer simulations to provide atomistic insights into the mechanisms and thermodynamics of protein–ligand and protein–protein binding. This information can then be used to guide the discovery and design of novel small molecule or peptide-based therapeutics addressing a variety of infectious and proliferative diseases. A major goal is to understand and address drug resistance in cancer.