Biomolecular modeling, cellular signaling and computer-aided drug design
Our research is focused on the development of novel theoretical and computational methods that accelerate modern computer simulations by orders of magnitude and the application of these methods in advanced biomolecular and cellular modeling and computer-aided drug design. In collaboration with leading experimental groups, we combine complementary simulations and experiments on in-depth studies and drug discovery of functionally important biomolecules and cellular signaling pathways.
At the interface of computational biology, chemistry and pharmacology, our research addresses three major topics: (i) Computer-aided drug design of G-protein-coupled receptors (GPCRs) and other important targets, (ii) method development for enhanced simulations of biomolecular diffusion and recognition in crowded cellular environments, and (iii) multiscale modeling of cellular signaling pathways that are relevant to neurological disorders, heart failure and cancer.
Representative Publications (*(co)-correspondence-authored, #Equal contributions):
- Miao, Y.* and McCammon, J. A. (2016). G-protein coupled receptors: advances in simulation and drug discovery. Current Opinion in Structural Biology, 41: 83-89.
- Miao, Y.* and McCammon, J.A. (2016) Unconstrained Enhanced Sampling for Free Energy Calculations of Biomolecules: A Review. Molecular Simulation. 42: 1046-1055.
- Miao, Y.* and McCammon, J. A. (2016b) Graded activation and free energy landscapes of a muscarinic G protein-coupled receptor. Proc Natl Acad Sci U S A, 113(43): 12162–12167.
- Miao, Y.*#, Goldfeld D., Moo E.V., Sexton P.M., Christopoulos A., McCammon, J. A.* and Valant, C.*# (2016a) Accelerated structure-based design of chemically diverse allosteric modulators of a muscarinic G protein-coupled receptor. Proc Natl Acad Sci U S A, 113(38): E5675–E5684.
- Pang, Y.T.#, Y. Miao#,*, Y. Wang* and J. A. McCammon* (2017) Gaussian accelerated molecular dynamics in NAMD, J Chemical Theory and Computation, 13(1): 9-19.
- Miao, Y.*, Feher V. and McCammon J.A. (2015) Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation. J Chemical Theory and Computation, 11(8): 3584-3595.
- Miao, Y.*#, F. Feixas*#, C. Eun*# and J. A. McCammon (2015) Accelerated molecular dynamics simulations of protein folding. J. Comp. Chem., 36(20): 1536-1549.
- Kappel, K., Miao, Y.* and McCammon J. A. (2015). Accelerated Molecular Dynamics Simulations of Ligand Binding to a Muscarinic G-protein Coupled Receptor. Quarterly Reviews of Biophysics (Discovery Report), 48 (04), 479-487.
- Miao, Y*, Nichols S.E., Gasper P.M., Metzger V.T., McCammon J.A. (2013) Activation and dynamic network of the M2 muscarinic receptor. Proc Natl Acad Sci USA 110(27): 10982-10987.
- Miao, Y, Z. Yi, D. Glass, L. Hong, M. Tyagi, J. Baudry, N. Jain and J. C. Smith (2012), Temperature-dependent Dynamical Transitions of Different Classes of Amino Acid Residue in a Globular Protein, J. Am. Chem. Soc., 134(48): 19576-19579.
- Miao, Y, Z. Yi, C. Cantrell, D. Glass, J. Baudry, N. Jain and J. C. Smith (2012), Coupled Flexibility Change in Cytochrome P450cam Substrate Binding Determined by Neutron Scattering, NMR and Molecular Dynamics Simulation, Biophysical J., 103(10): 2167-2176.
- Miao, Y, J. E. Johnson and P. J. Ortoleva (2010), All-atom Multiscale Simulation of Cowpea Chlorotic Mottle Virus Capsid Swelling, J. Phys. Chem. B, 114(34), 11181–11195.