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.
- "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)
- "Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum model," Kollman, Peter A., Irina Massova, Carolina Reyes, Bernd Kuhn, Shuanghong Huo, Lillian Chong, Matthew Lee et al, Accounts of chemical research 33, no. 12 (2000)
- "Molecular dynamics and free-energy calculations applied to affinity maturation in antibody 48G7," Chong, Lillian T., Yong Duan, Lu Wang, Irina Massova, and Peter A. Kollman, Proceedings of the National Academy of Sciences 96, no. 25 (1999)
- "Computation of electrostatic complements to proteins: A case of charge stabilized binding," Chong, Lillian T., Sara E. Dempster, Zachary S. Hendsch, Lee‐Peng Lee, and Bruce Tidorm, Protein science 7, no. 1 (1998)
- "Reaching biological timescales with all-atom molecular dynamics simulations," Zwier, Matthew C., and Lillian T. Chong, Current opinion in pharmacology 10, no. 6 (2010)
- "Simulations of the alternating acce4ss mechanism of the sodium symporter Mhp1," Adelman, J.L., Dale, A.L., Zwier, M.C., Bhatt, D., Chong, L.T., Zuckerman, D.M., Grabe, M., Biophysical Journal 101, no. 10 (2011)
- "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).
- “Flexibility vs. Preorganization: Direct Comparison of Binding Kinetics for a Disordered Peptide and its Exact Preorganized Analogues,” A. S. Saglam, D. W. Wang, M. C. Zwier and L. T. Chong, J. Phys. Chem. B,121, 10046 (2017).
- "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,” Daniel M. Zuckerman and Lillian T. Chong, Ann. Rev. Biophys., 46, 43 (2017).