Center for Computational Biology
University of Kansas
Accelerated Biomolecular Simulations and Drug Discovery
Remarkable advances of supercomputing are transforming computational chemistry and biology in studies of molecules to cells. However, large gaps remain between the time scales of supercomputer simulations (typically microseconds) and those of biological processes (milliseconds or even longer). To bridge these gaps, our research is focused on the development of novel theoretical and computational algorithms, notably Gaussian accelerated molecular dynamics (GaMD)1, Ligand GaMD (LiGaMD)2, Peptide GaMD (Pep-GaMD)3 and Protein-Protein Interaction GaMD (PPI-GaMD)4. These methods have unprecedentedly enabled microsecond atomic simulations to capture repetitive dissociation and binding of small-molecule ligands, highly flexible peptides and proteins, thereby allowing for highly efficient and accurate calculations of the biomolecular binding free energies and kinetics. We apply these methods in advanced modeling of biomolecular dynamics and cellular signaling processes. Systems of our interest include ligand/drug binding, peptide binding and protein-protein/membrane/nucleic acid interactions. In collaboration with leading experimental groups, we combine complementary simulations and experiments on in-depth studies and drug discovery of important biomolecules, including G-protein-coupled receptors (GPCRs) that serve as targets of ~1/3 of currently marketed drugs5-7, γ-secretase (a key membrane-embedded protease implicated in Alzheimer’s diseases)8 and RNA9.
1 J. Wang, P. Arantes, A. Bhattarai et al., WIREs Computational Molecular Science (2021) e1521.
2 Y. Miao, A. Bhattarai, and J. Wang, J Chem Theory Comput 16 (2020) 5526.
3 J. Wang, and Y. Miao, The Journal of Chemical Physics 153 (2020) 154109.
4 J. Wang, and Y. Miao, bioRxiv (2021) 2021.09.27.461974.
5 A. Bhattarai, J. Wang, and Y. Miao, BBA - General Subjects 1864 (2020) 129615.
6 C. J. Draper-Joyce, R. Bhola, J. Wang et al., Nature 597 (2021) 571.
7 S. Pawnikar, B. S. Magenheimer, E. Nevarez-Munoz et al., bioRxiv (2021) 2021.08.05.455255.
8 A. Bhattarai, S. Devkota, S. Bhattarai et al., ACS central science 6 (2020) 969.
9 Z. Tang, S. Akhter, A. Ramprasad et al., Nucleic Acids Res 49 (2021) 7870.
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Host: Dima Kozakov