Our research is focused on the use of molecular simulations to characterize the free energy landscapes and kinetics of a variety of biological processes, including large protein conformational transitions and protein binding. We have also been developing simulation strategies for aiding the design of protein-based conformational switches. Finally, we are developers of an upcoming AMBER force field and https://westpa.github.io/westpa/, a freely available, highly scalable software implementation of weighted ensemble path sampling strategies for the simulation of rare events (e.g. protein folding and protein binding).
Our research falls into the following main areas:
1) Development of weighted ensemble path sampling strategies and software for the efficient sampling of rare events (e.g. protein folding and binding) with rigorous kinetics.
2) Application of molecular simulations to investigate the mechanisms of protein conformational transitions, binding, and assembly processes.
3) Development of molecular simulation strategies for aiding the design of protein conformational switches.
4) Development of biomolecular force fields.
"Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models" Kollman, P.A., Massova, I., Reyes, C., (...), Case, D.A., Cheatham III., T.E. Accounts of Chemical Research
"The Amber biomolecular simulation programs" Case, D.A., Cheatham III, T.E., Darden, T., (...), Wang, B., Woods, R.J. Journal of Computational Chemistry 26(16), pp. 1668-1688
"GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit" Kollman, P.A., Massova, I., Reyes, C., (...), Case, D.A., Cheatham III., T.E. Accounts of Chemical Research
"Docking and scoring in virtual screening for drug discovery: Methods and applications" Kitchen, D.B., Decornez, H., Furr, J.R., Bajorath, J. 2004 Nature Reviews Drug Discovery
"Exploring Protein Native States and Large-Scale Conformational Changes with a Modified Generalized Born Model" Onufriev, A., Bashford, D., Case, D.A. Proteins: Structure, Function and Genetics
"Evaluating the Strength of Salt Bridges: A Comparison of Current Biomolecular Force Fields," K T Debiec, A M Gronenborn, and L T Chong. Journal of Physical Chemistry B 123.19 (2019)
"Large enhancement of response times of a protein conformational switch by computational design," Alex J. DeGrave, Jeung-Hoi Ha, Stewart N. Loh & Lillian T. Chong, Nature Commnications, 9, 1013 (2018).
"Integrating NMR, SAXS, and Atomistic Simulations: Structure and Dynamics of a Two-Domain Protein." Debiec, K.T., Whitley, M.J., Koharudin, L.M.I., Chong, L.T., Gronenborn, A.M. Biophysical Journal 114(4), pp. 839-855. (2018).
"WESTPA 2.0 Advances in Sampling, Storage, and Analysis of Weighted Ensemble Simulations," AJ Pratt, D M Zuckerman, and L T Chong. Biophysical Journal 114.3 (2018)
"Links between the charge model and bonded parameter force constants in biomolecular force fields." Cerutti, D.S., Debiec, K.T., Case, D.A., Chong, L.T. Journal of Chemical Physics 147(16),161730. (2017).
"Weighted Ensemble Simulation: Review of Methodology, Applications, and Software (Review)," Zuckerman, D.M., Chong, L.T., Annual Review of Biophysics 46, 43 (2017)
"Path-sampling strategies for simulating rare events in biomolecular systems," Chong, L.T., Saglam, A.S., Zuckerman, D.M., Current Opinion in Structural Biology 43, 88, (2017)
"Efficient Atomistic Simulation of Pathways and Calculation of Rate Constants for a Protein-Peptide Binding Process: Application to the MDM2 Protein and an Intrinsically Disordered p53 Peptide," Zwier, M.C., Pratt, A.J., Adelman, J.L., Kaus, J.W., Zuckerman, D.M., Chong, L.T., J. Phys. Chem. Lett 7, 3440 (2016)
"Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model," Debiec, K.T., Cerutti, D.S., Baker, L.R., Gronenborn, A.M., Case, D.A., Chong, L.T., J. Chem. Theory Comput. 12, 3926 (2016)
"Highly Efficient Computation of the Basal kon using Direct Simulation of Protein-Protein Association with Flexible Molecular Models," Saglam, A.S., Chong, L.T., J. Phys. Chem. B 120, 117 (2016)