Develop Novel and Innovative λ-Dynamics Based Methodologies
Perform in silico Structure-Based Drug Design
Investigate Aberrant Protein Side Chain Mutations in Disease Targets
Protein side chain mutations are fundamental to a variety of biological processes, including evolution, protein-engineering, and disease. The Vilseck lab uses λ-dynamics based techniques and molecular simulations to better understand the structural and functional effects of aberrant protein side chain mutations in disease targets and design novel pharmaceutical agents capable of addressing the ongoing healthcare concerns they cause. A major goal of the Vilseck lab is to understand drug resistance in cancer, specifically in multiple myeloma (MM) and in triple negative breast cancer (TNBC), essential pillars in the Precision Health Initiative at IU School of Medicine.
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.
Ding, X.; Vilseck, J. Z.; Brooks, C. L. III A Fast Solver for Large Scale Multistate Bennett Acceptance Ratio Equations. J. Chem. Theory Comput. 2019, 15, 799-802.
Hayes, R. L.; Vilseck, J. Z.; Brooks, C. L. III Approaching Protein Design with Multisite λ Dynamics: Accurate and Scalable Mutational Folding Free Energies in T4 Lysozyme. Protein Sci. 2018, 27, 1910-1922.
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.
Cabeza de Vaca, I.; Qian, Y.; Vilseck, J. Z.; Tirado-Rives, J.; Jorgensen, W. L., Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding. J. Chem. Theory Comput. 2018, 14, 3279-3288.
Ding, X.; Hayes, R. L.; Vilseck, J. Z.; Charles, M. K.; Brooks, C. L., III CDOCKER and λ-dynamics for prospective prediction in D3R Grand Challenge 2. J. Comput.-Aided Mol. Des. 2017, 32, 89-102.
Ding, X.; Vilseck, J. Z.; Hayes, R. L.; Brooks, C. L., III Gibbs Sampler-Based λ-Dynamics and Rao-Blackwell Estimator for Alchemical Free Energy Calculations. J. Chem. Theory Comput. 2017, 13, 2501-2510.