Department of Chemistry



Lillian Chong



331 Eberly Hall
Chevron Science Center
219 Parkman Avenue

Pittsburgh, PA 15260

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Research Overview

Computational Biophysics; Biomolecular simulations

Research in the Chong lab involves the development and application of molecular simulation approaches to model a variety of biophysical processes. A summary of some of our research directions is provided below.

Weighted ensemble approaches for sampling rare events

To enable the efficient simulation of rare events (e.g. protein folding and binding processes), we have been developing approaches based on “weighted ensemble” path sampling, which introduces no bias into the dynamics. Using our high-performance implementation of this approach (WESTPA), we and others have demonstrated that this approach can enhance the efficiency of generating pathways and rate constants for rare events by orders of magnitude

Simulation of protein binding pathways and kinetics

Obtaining atomically detailed views of protein binding (and unbinding) processes has been a grand challenge in the field of biomolecular simulation due to the long timescales required. To tackle this difficult problem, we have been using weighted ensemble algorithms to generate pathways and rate constants for various protein binding processes, including those that involve intrinsically disordered peptides that fold only upon binding their intended partner proteins.

Design of protein conformational switches

The process of designing protein conformational switches involves a significant amount of educated guesswork in the laboratory. To aid in the rational design of protein switches, we have been developing simulation approaches with various levels of coarse-graining to efficiently predict the dynamics of these protein switches. We have been focusing on a particular class of protein-based switches that are engineered using a "mutually exclusive folding" strategy in which two formerly independent protein domains are fused together in such a way that at any moment in time, only one or the other protein can be folded, but not both.


  • University of Pittsburgh Arts & Sciences Bellet Teaching Excellence Award, 2017
  • National Science Foundation CAREER Award, 2009-2014
  • Carnegie Science Emerging Female Scientist Award, 2012
  • Hewlett-Packard Outstanding Junior Faculty Award, 2008
  • Frank M. Goyan Graduate Research Award in Physical Chemistry at UCSF, 2002
  • Burroughs Wellcome Graduate Research Fellowship, 2001-2002
  • National Science Foundation Graduate Research Fellowship, 1998-2001


“A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics,” AT Bogetti, HE Piston, JMG Leung, CC Cabalteja, DT Yang, AJ DeGrave, KT Debiec, DS Cerutti, DA Case, WS Horne, and LT Chong J. Chem. Phys. 2020, 153 6, 064101
“A suite of tutorials for the WESTPA rare-events sampling software,” AT Bogetti, B Mostofian, A Dickson, AJ Pratt, AS Saglam, PO Harrison, JL Adelman, M Dudek, PA Torrillo, AJ DeGrave, U Adhikari, MC Zwier, DM Zuckerman, and LT Chong,  LiveCoMS 2019, 1 2, 10607
“Large enhancement of response times of a protein conformational switch by computational design,” AJ DeGrave, JH Ha, SN Loh, and LT Chong, Nat. Commun. 2018, 9, 1013
“Links Between the Charge Model and Bonded Parameter Force Constants in Biomolecular Force Fields,” Ceruitt DS, Deibiec KT, Case DA, and Chong LT J. Chem. Phys. 2017, 147, 161730
“Flexibility vs. Preorganization: Direct Comparison of Binding Kinetics for a Disordered Peptide and its Exact Preorganized Analogues,” Saglam AS, Wang DW, Zwier MC, and Chong LT J. Phys. Chem. B 2017, 121, 10046-10054
“Weighted Ensemble Simulation: Review of Methodology, Applications, and Software,” Zuckerman DM and Chong LT Ann. Rev. Biophys. 2017, 46, 43-57
“Path-Sampling Strategies for Simulating Rare Events in Biomolecular Systems,” Chong LT, Saglam AS, and Zuckerman DM Curr. Opin. Struct. Biol. 2017, 43, 88-94
“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 MC, Pratt AJ, Adelman JL, Kaus JW, Zuckerman DM, and Chong LT J. Phys. Chem. Lett. 2016, 7, 3440-3445
“Further Along the Road Less Traveled: AMBER ffl5iqp, An Original Protein Force Field Built on a Self-Consistent Physical Model,” Deibiec KT, Cerutti DS, Baker LR, Gronenborn AM, Case DA, and Chong LT J. Chem. Theory Comput. 2016, 12, 3926-3947
“Highly Efficient Computation of the Basal kon Using Direct Simulation of Protein-Protein Association with Flexible Molecular Models,” Saglam AS and Chong LT J. Phys. Chem. B 2016, 120, 117-122
“Estimating First-Passage Time Distributions from Weighted Ensemble Simulations and non-Markovian Analyses,” Suárez E, Pratt AJ, Chong LT, and Zuckerman DM Protein Sci. 2016, 25, 67-78
“WESTPA: An Interoperable, Highly Scalable Software Package for Weighted Ensemble Simulation and Analysis,” Zwier MC, Adelman JL, Kaus JW, Pratt AJ, Wong KF, Rego NB, Suárez E, Lettieri S, Wand DW, Grabe M, Zuckerman DM, and Chong LT J. Chem. Theory Comput. 2015, 11, 800-809
“Simultaneous computation of dynamical and equilibrium information using a weighted ensemble of trajectories,” Suarez, E.; Lettieri, S.; Zwier, M. C.; Stringer, C. A.; Subramanian, S. R.; Chong, L. T.; and Zuckerman, D. M. J. Chem. Theory Comput. 2014, 10, 2658-2667
“Evaluating the strength of salt bridges - a comparison of current biomolecular force fields,” Debiec, K. T.; Gronenborn, A. M.; and Chong, L. T. J. Phys. Chem. B 2014, 118, 6561-6569
“Effects of high temperature on desolvation costs of salt bridges across protein binding interfaces: Similarities and differences between implicit and explicit solvent models.,” R Salari and LT Chong J. Phys. Chem. B 2012, 116, 2561-2567
“The Native GCN4 Leucine-Zipper Domain Does Not Uniquely Specify a Dimeric Oligomerization State,” Oshaben KM, Salari R, McCaslin DR, Chong LT, and Horne WS Bio Chem. 2012, 51, 9581-9591
“Simulations of the alternating access mechanism of the sodium symporter Mhp1,” Adelman JL, Scarbrough A, Zwier MC, Bhatt D, Chong LT, Zuckerman DM, and Grabe M Biophys. J. 2011, 101, 2399-2407
“Direct observations of shifts in the beta-sheet register of a protein-peptide complex using explicit solvent simulations.,” Panteva MT,* Salari R,*Bhattacharjee M, and Chong LT.*equal authorship Biophysical Journal 2011, 100, L50-L52
“Direct observations of conformational distributions of intrinsically disordered p53 peptides using UV raman and explicit solvent simulations.,” Xiong K, Zwier MC, Myshakina NS, Burger VM, Asher SA, and Chong LT. J. Phys. Chem. A 2011, 115, 9520-9527
“Efficient explicit-solvent molecular dynamics simulations of molecular associations: Methane/methane, Na+/Cl-, methane/benzene, and K+/18-crown-6 ether,” Zwier MC, Kaus JW, and Chong LT. J. Chem. Theory and Computation 2011, 7, 1189-1197
“Molecular simulations of mutually exclusive folding in a two-domain protein switch.,” Mills, B. M. and Chong L. T. Biophys. J. 2011, 100, 756-764
“Desolvation Costs of Salt Bridges across Protein Binding Interfaces: Similarities and Differences between Implicit and Explicit Solvent Models,” Salari R. and Chong L. T. J. Phys. Chem. Lett. 2010, 1, 2844-2848
“Reaching biological timescales with all-atom molecular dynamics simulations,” Zwier, M. C. and Chong L. T. Curr. Opin. Pharmacol. 2010, 10, 745-752
“Effect of Interdomain Linker Length on an Antagonistic Folding-Unfolding Equilibrium between Two Protein Domains,” Cutler, T. A.; Mills B. M.; Lubin D. J.; Chong, L.T.; and Loh S. N. J. Mol. Biol. 2009, 386, 854-868