Weighted ensemble simulation of rare events

JD Russo*, S Zhang*, JMG Leung*, AT Bogetti*, JP Thompson, AJ DeGrave, PA Torrillo, AJ Pratt, KF Wong, J Xia, J Copperman, JL Adelman, MC Zwier, DN LeBard, DM Zuckerman, LT Chong. “WESTPA 2.0: High-Performance Upgrades for Weighted Ensemble Simulations and Analysis of Longer-Timescale Applications.” J. Chem. Theory Comput. 2022, 18 (2), 638–649. *equal authorship link pdf

S Zhang, JP Thompson, J Xia, AT Bogetti, F York, AG Skillman, LT Chong, DN LeBard. “Mechanistic Insights into Passive Membrane Permeability of Drug-Like Molecules from a Weighted Ensemble of Trajectories.” J. Chem. Inf. Model 2022. link pdf

T Sztain, S Ahn, AT Bogetti, L Casalino, JA Goldsmith, E Seitz, RS McCool, FL Kearns, F Acosta-Reyes, S Maji, G Mashayekhi, JA McCammon, A Ourmazd, J Frankm, JS McLellan, LT Chong*, and RE Amaro*. “A glycan gate controls opening of the SARS-CoV-2 spike protein.” Nat. Chem. 2021. *co-corresponding authors link pdf

AJ DeGrave*, AT Bogetti*, and LT Chong. “The RED scheme: Rate-constant estimation from pre-steady state weighted ensemble simulations.” bioRxiv 2021. *equal authorship link pdf

PA Torrillo*, AT Bogetti*, and LT Chong. “A minimal, adaptive binning scheme for weighted ensemble simulations.” J. Chem. Phys. A 2021, 125: 1642–1649. *equal authorship link pdf

L Casalino, A Dommer, Z Gaieb, EP Barros, T Sztain, S Ahn, A Trifan, A Brace, AT Bogetti, H Ma, H Lee, M Turilli, S Khalid, LT Chong, C Simmerling, DJ Hardy, JDC Maia, JC Phillips, T Kurth, A Stern, L Huang, J McCalpin, M Tatineni, T Gibbs, JE Stone, S Jha, A Ramanathan, and RE Amaro. “AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics.” bioRxiv 2020.
link pdf This paper has been awarded the Gordon Bell Special Prize.

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. “A suite of tutorials for the WESTPA rare-events sampling software.” Living J. Comput. Mol. Sci. 2019, 1, 10607. *equal authorship link pdf

AS Saglam and LT Chong. “Protein-protein binding pathways and calculations of rate constants using fully-continuous, explicit-solvent simulations.” Chem. Sci. 2019, 10, 2360. link pdf data

AJ DeGrave, JH Ha, SN Loh, and LT Chong. “Large enhancement of response times of a protein conformational switch by computational design.” Nat. Commun. 2018, 9, 1013. link pdf

AS Saglam, DW Wang, MC Zwier, and LT Chong. “Flexibility vs preorganization: Direct comparison of binding kinetics for a disordered peptide and its exact preorganized analogues.” J. Phys. Chem. B 2017, 121, 10046. link pdf

DM Zuckerman and LT Chong. “Weighted ensemble simulation: Review of methodology, applications, and software.” Ann. Rev. Biophys. 2017, 46, 43. link pdf

LT Chong, AS Saglam, and DM Zuckerman. “Path-sampling strategies for simulating rare events in biomolecular systems.” Curr. Opin. Struct. Biol. 2017, 43, 88. link pdf

MC Zwier, AJ Pratt, JL Adelman, JW Kaus, DM Zuckerman, and LT Chong. “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.” J. Phys. Chem. Lett. 2016, 7, 3440. link pdf

AS Saglam and LT Chong. “Highly efficient computation of the basal kon using direct simulation of protein-protein association with flexible molecular models.” J. Phys. Chem. B 2016, 120, 117. link pdf

E Suárez, AJ Pratt, LT Chong, and DM Zuckerman. “Estimating first-passage time distributions from weighted ensemble simulations and non-Markovian analyses.” Prot. Sci. 2016, 25, 67. link pdf

MC Zwier, JL Adelman, JW Kaus, AJ Pratt, KF Wong, NB Rego, E Suárez, S Lettieri, DW Wang, M Grabe, DM Zuckerman, and LT Chong. “WESTPA: An interoperable, highly scalable software package for weighted ensemble simulation and analysis” J. Chem. Theory Comput. 2015,11, 800. link pdf

E Suárez, S Lettieri, MC Zwier, CA Stringer, SR Subramanian, LT Chong, and DM Zuckerman. “Simultaneous computation of dynamical and equilibrium information using a weighted ensemble of trajectories.” J. Chem. Theory Comput. 2014, 10, 2658. link pdf

MC Zwier, JW Kaus, and LT Chong. “Efficient explicit-solvent molecular dynamics simulations of molecular associations: Methane/methane, Na+/Cl-, methane/benzene, and K+/18-crown-6 ether.” J. Chem. Theory Comput. 2011, 7, 1189. link pdf

JL Adelman, A Scarbrough, MC Zwier, D Bhatt, LT Chong, DM Zuckerman, and M Grabe. “Simulations of the alternating access mechanism of the sodium symporter Mhp1.” Biophys. J. 2011, 101, 2399. link pdf

MC Zwier and LT Chong. “Reaching biological timescales with all-atom molecular dynamics simulations.” Curr. Opin. Pharmacol. 2010, 10, 745-752. link pdf

Development of biomolecular force fields

DT Yang, AM Gronenborn, and LT Chong. “Development and Validation of Fluorinated, Aromatic Amino Acid Parameters for Use with the AMBER ff15ipq Protein Force Field” J. Phys. Chem. A 2022, 126, 2286-2297. link pdf code

AT Bogetti*, HE Piston*, JMG Leung*, CC Cabalteja, DT Yang, AJ DeGrave, KT Debiec, DS Cerutti, DA Case, WS Horne, and LT Chong. “A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics.” J. Chem. Phys. 2020, 153(6), 064101. *equal authorship link pdf

DS Cerutti, KT Debiec, DA Case, and LT Chong. “Links between the charge model and bonded parameter force constants in biomolecular force constants.” J. Chem. Phys. 2017, 147, 161730. link pdf

KT Debiec, DS Cerutti, LR Baker, AM Gronenborn, DA Case, and LT Chong. “Further along the road less traveled: AMBER ff15ipq, an original protein force field built on a self-consistent physical model.” J. Chem. Theory Comput. 2016, 12, 3926. link pdf

KT Debiec, AM Gronenborn, and LT Chong. “Evaluating the strength of salt bridges - a comparison of current biomolecular force fields.” J. Phys. Chem. B 2014, 118, 6561. link pdf

R Salari and LT Chong. “Effects of increasing temperature on desolvation costs of salt bridges across protein binding interfaces: Similarities and differences between implicit and explicit solvent models.” J. Phys. Chem. B 2012, 116, 2561. link pdf

R Salari and LT Chong. “Desolvation costs of salt bridges across protein binding interfaces: Similarities and differences between implicit and explicit solvent models.” J. Phys. Chem. Lett. 2010, 1, 2844. link pdf

Design of protein conformational switches

AT Bogetti, MF Presti, SN Loh, and LT Chong. “The Next Frontier for Designing Switchable Proteins: Rational Enhancement of Kinetics.” J. Phys. Chem. B 2021, 125 (32), 9069–9077. link pdf

AJ DeGrave, JH Ha, SN Loh, and LT Chong. “Large enhancement of response times of a protein conformational switch by computational design.” Nat. Commun. 2018, 9, 1013. link pdf

BM Mills and LT Chong. “Molecular simulations of mutually exclusive folding in a two-domain protein switch.” Biophys. J. 2011, 100, 756. link pdf

TA Cutler, BM Mills, DJ Lubin, LT Chong, and SN Loh. “Effect of interdomain linker length on an antagonistic folding-unfolding equilibrium between two protein domains.” J. Mol. Biol. 2009, 386, 854. link pdf

Large-scale “brute-force” simulation studies

KT Debiec, MJ Whitley, LMI Koharudin, LT Chong, and AM Gronenborn. “Integrating NMR, SAXS, and Atomistic Simulations: Structure and Dynamics of a Two-Domain Protein.” Biophys. J. 2018, 114, 839. link pdf

KM Oshaben, R Salari, DR McCaslin, LT Chong, and WS Horne. “The native GCN4 leucine-zipper domain does not uniquely specify a dimeric oligomerization state.” Biochemistry 2012, 51, 9581. link pdf

MT Panteva*, R Salari*, M Bhattacharjee, and LT Chong. “Direct observations of shifts in the beta-sheet register of a protein-peptide complex using explicit solvent simulations.” Biophys. J. Letters 2011, 100, L50. *equal authorship link pdf

K Xiong, MC Zwier, NS Myshakina, VM Burger, SA Asher, and LT Chong. “Direct observations of conformational distributions of intrinsically disordered p53 peptides using UV Raman and explicit solvent simulations.” J. Phys. Chem. A 2011, 115, 9520. link pdf

“Pre-Chong Lab”

LT Chong, JW Pitera, WC Swope, and VS Pande. “Comparison of computational approaches for predicting the effects of missense mutations on p53 function.” J. Mol. Graph. Model. 2009, 27, 978. link pdf

LT Chong, WC Swope, JW Pitera, and VS Pande. “Kinetic computational alanine scanning: application to p53 oligomerization.” J. Mol. Biol. 2006, 257, 1039. link pdf

LT Chong, CD Snow, YM Rhee, and VS Pande. “Dimerization of the p53 oligomerization domain: Identification of a folding nucleus by molecular dynamics simulations.” J. Mol. Biol. 2005, 345, 869. link pdf

LT Chong, P Bandyopadhyay, TS Scanlan, ID Kuntz, and PA Kollman. “Direct Hydroxide Attack is a Plausible Mechanism for Amidase Antibody 43C9.” J. Comp. Chem. 2003, 4, 1371. link pdf

TS Lee*, LT Chong*, JD Chodera, and PA Kollman. “An Alternative Explanation for the Catalytic Proficiency of Orotidine 5’-Phosphate Decarboxylase.” J. Am. Chem. Soc. 2001, 123, 12837. *equal authorship link pdf

PA Kollman, I Massova, C Reyes, B Kuhn, S Huo, LT Chong, MR Lee, TS Lee, Y Duan, W Wang, O Donini, P Cieplak, J Srinivasan, D Case, and TE Cheatham 3rd. “Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models.” Acc. Chem. Res. 2000, 33, 889. link pdf

LT Chong, Y Duan, L Wang, I Massova, and PA Kollman. “Molecular Dynamics Simulation and Free Energy Calculations Applied to Affinity Maturation in Antibody 48G7.” Proc. Natl. Acad. Sci. USA 1999, 96, 14330. link pdf

K Lin, HS Ateeq, SH Hsiung, LT Chong, CN Zimmerman, A Castro, WC Lee, CE Hammond, S Kalkunte, LL Chen, RB Pepinsky, DR Leone, AG Sprague, WM Abraham, A Gill, RR Lobb, and SP Adams. “Selective, Tight-binding Inhibitors of Integrin Alpha-4-beta-1 that Inhibit Allergic Airway Responses.” J. Med. Chem. 1999, 42, 920. link pdf

LT Chong, SE Dempster, ZS Hendsch, L-P Lee, and B Tidor. “Computation of Electrostatic Complements to Proteins: A Case of Charge Stabilized Binding.” Protein Sci. 1998, 7, 206. link pdf