Dr. Yinglong Miao, University of Kansas
Abstract: Biomolecular recognition plays key roles in cellular signaling. It is critical to quantify thermodynamics and kinetics of biomolecular binding for effective therapeutic design. However, such tasks have proven challenging in computational chemistry and biology. Building on a robust Gaussian accelerated molecular dynamics (GaMD) technique, we have developed new Ligand GaMD (LiGaMD)1, Peptide GaMD (Pep-GaMD)2 and Protein-Protein Interaction GaMD (PPI-GaMD)3 algorithms. They 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. In addition, I will talk about recent applications of GaMD and ensemble docking in simulations and drug discovery of flexible biomolecules, in particular G-protein-coupled receptors (GPCRs)4, 5.
References:
1. Y. Miao, A. Bhattarai, and J. Wang, J Chem Theory Comput 16 (2020) 5526.
2. J. Wang, and Y. Miao, The Journal of Chemical Physics 153 (2020) 154109.
3. J. Wang, and Y. Miao, bioRxiv (2021) 2021.09.27.461974.
4. A. Bhattarai, J. Wang, and Y. Miao, BBA - General Subjects 1864 (2020) 129615.
5. C. J. Draper-Joyce, R. Bhola, J. Wang et al., Nature 597 (2021) 571.