Enhanced Configurational Sampling Approaches to Alchemical Ligand Binding Free Energy Simulations: Current Status and Challenges

Jiang, Wei

doi:10.1021/acs.jpcb.3c02020

Enhanced Configurational Sampling Approaches to Alchemical Ligand Binding Free Energy Simulations: Current Status and Challenges

Journal Article · Thu Jul 27 00:00:00 EDT 2023 · Journal of Physical Chemistry. B

DOI:https://doi.org/10.1021/acs.jpcb.3c02020· OSTI ID:2352640

^[1]

Argonne National Laboratory (ANL), Argonne, IL (United States)

In this study, ligand binding free energy simulations (LB-FES) have been routine tasks in modern drug discovery campaign. A long-standing challenge for LB-FES is the difficulty in adequately sampling nontrivial environmental reorganizations in response to ligand binding. Therefore, various enhanced configurational sampling (ECS) approaches were devised to speed up fluctuations of relevant slow degrees of freedom (SDOF) and ensure simulation convergence. However, in contrast to the achievements in parametrization, software performance, and workflow automation, efficient ECS methodology suitable for high throughput screening remains in an early stage of development. Here, a review of ECS developments with LB-FES is presented, revisiting current approaches and underlining the major technical pitfalls and challenges. This Perspective focuses on alchemical LB-FES on account of their predominant role in high throughput drug screening as well as the established partnership with ECS. The critical aspects of designing ECS approaches, from both theoretical and applied perspectives, are described. This work is intended to provide a contemporary review of the scientific, technical, and practical issues associated with the accelerating convergence of alchemical LBFES.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2352640

Journal Information:: Journal of Physical Chemistry. B, Journal Name: Journal of Physical Chemistry. B Journal Issue: 31 Vol. 127; ISSN 1520-6106

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (57)

Orthogonal sampling in free-energy calculations of residue mutations in a tripeptide: TI versusλ-LEUS Bieler, Noah S.; Hünenberger, Philippe H. Journal of Computational Chemistry, Vol. 36, Issue 22 https://doi.org/10.1002/jcc.23984	journal	July 2015
GENESIS 1.1: A hybrid-parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms Kobayashi, Chigusa; Jung, Jaewoon; Matsunaga, Yasuhiro Journal of Computational Chemistry, Vol. 38, Issue 25 https://doi.org/10.1002/jcc.24874	journal	July 2017
An overview of the Amber biomolecular simulation package: Amber biomolecular simulation package Salomon-Ferrer, Romelia; Case, David A.; Walker, Ross C. Wiley Interdisciplinary Reviews: Computational Molecular Science, Vol. 3, Issue 2 https://doi.org/10.1002/wcms.1121	journal	September 2012
A generic implementation of replica exchange with solute tempering (REST2) algorithm in NAMD for complex biophysical simulations Jo, Sunhwan; Jiang, Wei Computer Physics Communications, Vol. 197 https://doi.org/10.1016/j.cpc.2015.08.030	journal	December 2015
Generalized-ensemble algorithms: enhanced sampling techniques for Monte Carlo and molecular dynamics simulations Okamoto, Yuko Journal of Molecular Graphics and Modelling, Vol. 22, Issue 5 https://doi.org/10.1016/j.jmgm.2003.12.009	journal	May 2004
New developments in force fields for biomolecular simulations Nerenberg, Paul S.; Head-Gordon, Teresa Current Opinion in Structural Biology, Vol. 49 https://doi.org/10.1016/j.sbi.2018.02.002	journal	April 2018
Grand canonical Monte Carlo (GCMC) study on adsorption performance of metal organic frameworks (MOFs) for carbon capture Tao, Y. R.; Zhang, G. H.; Xu, H. J. Sustainable Materials and Technologies, Vol. 32 https://doi.org/10.1016/j.susmat.2021.e00383	journal	July 2022
Evolution of Alchemical Free Energy Methods in Drug Discovery Song, Lin Frank; Merz, Kenneth M. Journal of Chemical Information and Modeling, Vol. 60, Issue 11 https://doi.org/10.1021/acs.jcim.0c00547	journal	August 2020
Alchemical Binding Free Energy Calculations in AMBER20: Advances and Best Practices for Drug Discovery Lee, Tai-Sung; Allen, Bryce K.; Giese, Timothy J. Journal of Chemical Information and Modeling, Vol. 60, Issue 11 https://doi.org/10.1021/acs.jcim.0c00613	journal	September 2020
CHARMM-GUI LBS Finder & Refiner for Ligand Binding Site Prediction and Refinement Guterres, Hugo; Park, Sang-Jun; Zhang, Han Journal of Chemical Information and Modeling, Vol. 61, Issue 8 https://doi.org/10.1021/acs.jcim.1c00561	journal	July 2021
CHARMM-GUI Free Energy Calculator for Practical Ligand Binding Free Energy Simulations with AMBER Zhang, Han; Kim, Seonghoon; Giese, Timothy J. Journal of Chemical Information and Modeling, Vol. 61, Issue 9 https://doi.org/10.1021/acs.jcim.1c00747	journal	September 2021
Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations Cournia, Zoe; Allen, Bryce; Sherman, Woody Journal of Chemical Information and Modeling, Vol. 57, Issue 12 https://doi.org/10.1021/acs.jcim.7b00564	journal	December 2017
Heteroaryldihydropyrimidines Alter Capsid Assembly By Adjusting the Binding Affinity and Pattern of the Hepatitis B Virus Core Protein Liu, Huihui; Okazaki, Susumu; Shinoda, Wataru Journal of Chemical Information and Modeling, Vol. 59, Issue 12 https://doi.org/10.1021/acs.jcim.9b01010	journal	November 2019
Enhancing Water Sampling in Free Energy Calculations with Grand Canonical Monte Carlo Ross, Gregory A.; Russell, Ellery; Deng, Yuqing Journal of Chemical Theory and Computation, Vol. 16, Issue 10 https://doi.org/10.1021/acs.jctc.0c00660	journal	September 2020
Automated, Accurate, and Scalable Relative Protein–Ligand Binding Free-Energy Calculations Using Lambda Dynamics Raman, E. Prabhu; Paul, Thomas J.; Hayes, Ryan L. Journal of Chemical Theory and Computation, Vol. 16, Issue 12 https://doi.org/10.1021/acs.jctc.0c00830	journal	November 2020
CHARMM-GUI Free Energy Calculator for Absolute and Relative Ligand Solvation and Binding Free Energy Simulations Kim, Seonghoon; Oshima, Hiraku; Zhang, Han Journal of Chemical Theory and Computation, Vol. 16, Issue 11 https://doi.org/10.1021/acs.jctc.0c00884	journal	October 2020
Tinker-HP: Accelerating Molecular Dynamics Simulations of Large Complex Systems with Advanced Point Dipole Polarizable Force Fields Using GPUs and Multi-GPU Systems Adjoua, Olivier; Lagardère, Louis; Jolly, Luc-Henri Journal of Chemical Theory and Computation, Vol. 17, Issue 4 https://doi.org/10.1021/acs.jctc.0c01164	journal	March 2021
Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies Zou, Junjie; Li, Zhipeng; Liu, Shuai Journal of Chemical Theory and Computation, Vol. 17, Issue 6 https://doi.org/10.1021/acs.jctc.1c00214	journal	May 2021
Efficient Alchemical Intermediate States in Free Energy Calculations Using λ-Enveloping Distribution Sampling König, Gerhard; Ries, Benjamin; Hünenberger, Philippe H. Journal of Chemical Theory and Computation, Vol. 17, Issue 9 https://doi.org/10.1021/acs.jctc.1c00418	journal	September 2021
BLaDE: A Basic Lambda Dynamics Engine for GPU-Accelerated Molecular Dynamics Free Energy Calculations Hayes, Ryan L.; Buckner, Joshua; Brooks, Charles L. Journal of Chemical Theory and Computation, Vol. 17, Issue 11 https://doi.org/10.1021/acs.jctc.1c00833	journal	October 2021
Fast Equilibration of Water between Buried Sites and the Bulk by Molecular Dynamics with Parallel Monte Carlo Water Moves on Graphical Processing Units Ben-Shalom, Ido Y.; Lin, Charles; Radak, Brian K. Journal of Chemical Theory and Computation, Vol. 17, Issue 12 https://doi.org/10.1021/acs.jctc.1c00867	journal	November 2021
Large Scale Study of Ligand–Protein Relative Binding Free Energy Calculations: Actionable Predictions from Statistically Robust Protocols Bhati, Agastya P.; Coveney, Peter V. Journal of Chemical Theory and Computation, Vol. 18, Issue 4 https://doi.org/10.1021/acs.jctc.1c01288	journal	March 2022
Enhanced Grand Canonical Sampling of Occluded Water Sites Using Nonequilibrium Candidate Monte Carlo Melling, Oliver J.; Samways, Marley L.; Ge, Yunhui Journal of Chemical Theory and Computation, Vol. 19, Issue 3 https://doi.org/10.1021/acs.jctc.2c00823	journal	January 2023
CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field Lee, Jumin; Cheng, Xi; Swails, Jason M. Journal of Chemical Theory and Computation, Vol. 12, Issue 1 https://doi.org/10.1021/acs.jctc.5b00935	journal	December 2015
Predictive Sampling of Rare Conformational Events in Aqueous Solution: Designing a Generalized Orthogonal Space Tempering Method Lu, Chao; Li, Xubin; Wu, Dongsheng Journal of Chemical Theory and Computation, Vol. 12, Issue 1 https://doi.org/10.1021/acs.jctc.5b00953	journal	December 2015
Binding Energy Distribution Analysis Method: Hamiltonian Replica Exchange with Torsional Flattening for Binding Mode Prediction and Binding Free Energy Estimation Mentes, Ahmet; Deng, Nan-Jie; Vijayan, R. S. K. Journal of Chemical Theory and Computation, Vol. 12, Issue 5 https://doi.org/10.1021/acs.jctc.6b00134	journal	April 2016
Accurate Modeling of Scaffold Hopping Transformations in Drug Discovery Wang, Lingle; Deng, Yuqing; Wu, Yujie Journal of Chemical Theory and Computation, Vol. 13, Issue 1 https://doi.org/10.1021/acs.jctc.6b00991	journal	December 2016
Ensemble-Based Replica Exchange Alchemical Free Energy Methods: The Effect of Protein Mutations on Inhibitor Binding Bhati, Agastya P.; Wan, Shunzhou; Coveney, Peter V. Journal of Chemical Theory and Computation, Vol. 15, Issue 2 https://doi.org/10.1021/acs.jctc.8b01118	journal	December 2018
Accelerating Convergence of Free Energy Computations with Hamiltonian Simulated Annealing of Solvent (HSAS) Jiang, Wei Journal of Chemical Theory and Computation, Vol. 15, Issue 4 https://doi.org/10.1021/acs.jctc.8b01147	journal	March 2019
String Method for Protein–Protein Binding Free-Energy Calculations Suh, Donghyuk; Jo, Sunhwan; Jiang, Wei Journal of Chemical Theory and Computation, Vol. 15, Issue 11 https://doi.org/10.1021/acs.jctc.9b00499	journal	October 2019
Ligand-Binding-Site Structure Refinement Using Molecular Dynamics with Restraints Derived from Predicted Binding Site Templates Guterres, Hugo; Lee, Hui Sun; Im, Wonpil Journal of Chemical Theory and Computation, Vol. 15, Issue 11 https://doi.org/10.1021/acs.jctc.9b00751	journal	September 2019
Capturing the Flexibility of a Protein–Ligand Complex: Binding Free Energies from Different Enhanced Sampling Techniques Wingbermühle, Sebastian; Schäfer, Lars V. Journal of Chemical Theory and Computation, Vol. 16, Issue 7 https://doi.org/10.1021/acs.jctc.9b01150	journal	June 2020
Reduced Free Energy Perturbation/Hamiltonian Replica Exchange Molecular Dynamics Method with Unbiased Alchemical Thermodynamic Axis Jiang, Wei; Thirman, Jonathan; Jo, Sunhwan The Journal of Physical Chemistry B, Vol. 122, Issue 41 https://doi.org/10.1021/acs.jpcb.8b03277	journal	September 2018
Calculation of Standard Binding Free Energies: Aromatic Molecules in the T4 Lysozyme L99A Mutant Deng, Yuqing; Roux, Benoît Journal of Chemical Theory and Computation, Vol. 2, Issue 5 https://doi.org/10.1021/ct060037v	journal	July 2006
Free Energy Perturbation Hamiltonian Replica-Exchange Molecular Dynamics (FEP/H-REMD) for Absolute Ligand Binding Free Energy Calculations Jiang, Wei; Roux, Benoît Journal of Chemical Theory and Computation, Vol. 6, Issue 9 https://doi.org/10.1021/ct1001768	journal	July 2010
Practically Efficient and Robust Free Energy Calculations: Double-Integration Orthogonal Space Tempering Zheng, Lianqing; Yang, Wei Journal of Chemical Theory and Computation, Vol. 8, Issue 3 https://doi.org/10.1021/ct200726v	journal	February 2012
Calculation of Free Energy Landscape in Multi-Dimensions with Hamiltonian-Exchange Umbrella Sampling on Petascale Supercomputer Jiang, Wei; Luo, Yun; Maragliano, Luca Journal of Chemical Theory and Computation, Vol. 8, Issue 11 https://doi.org/10.1021/ct300468g	journal	October 2012
Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation Miao, Yinglong; Sinko, William; Pierce, Levi Journal of Chemical Theory and Computation, Vol. 10, Issue 7 https://doi.org/10.1021/ct500090q	journal	May 2014
Local Elevation Umbrella Sampling Applied to the Calculation of Alchemical Free-Energy Changes via λ-Dynamics: The λ-LEUS Scheme Bieler, Noah S.; Häuselmann, Rico; Hünenberger, Philippe H. Journal of Chemical Theory and Computation, Vol. 10, Issue 8 https://doi.org/10.1021/ct5002686	journal	July 2014
Confine-and-Release Method: Obtaining Correct Binding Free Energies in the Presence of Protein Conformational Change Mobley, David L.; Chodera, John D.; Dill, Ken A. Journal of Chemical Theory and Computation, Vol. 3, Issue 4 https://doi.org/10.1021/ct700032n	journal	May 2007
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation Hess, Berk; Kutzner, Carsten; van der Spoel, David Journal of Chemical Theory and Computation, Vol. 4, Issue 3 https://doi.org/10.1021/ct700301q	journal	February 2008
Replica-Exchange Accelerated Molecular Dynamics (REXAMD) Applied to Thermodynamic Integration Fajer, Mikolai; Hamelberg, Donald; McCammon, J. Andrew Journal of Chemical Theory and Computation, Vol. 4, Issue 10 https://doi.org/10.1021/ct800250m	journal	September 2008
Computation of Absolute Hydration and Binding Free Energy with Free Energy Perturbation Distributed Replica-Exchange Molecular Dynamics Jiang, Wei; Hodoscek, Milan; Roux, Benoît Journal of Chemical Theory and Computation, Vol. 5, Issue 10 https://doi.org/10.1021/ct900223z	journal	August 2009
Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field Wang, Lingle; Wu, Yujie; Deng, Yuqing Journal of the American Chemical Society, Vol. 137, Issue 7 https://doi.org/10.1021/ja512751q	journal	February 2015
Replica Exchange with Solute Scaling: A More Efficient Version of Replica Exchange with Solute Tempering (REST2) Wang, Lingle; Friesner, Richard A.; Berne, B. J. The Journal of Physical Chemistry B, Vol. 115, Issue 30 https://doi.org/10.1021/jp204407d	journal	August 2011
Generalized solvent boundary potential for computer simulations Im, Wonpil; Bernèche, Simon; Roux, Benoı̂t The Journal of Chemical Physics, Vol. 114, Issue 7 https://doi.org/10.1063/1.1336570	journal	February 2001
Grand canonical Monte Carlo simulations of water in protein environments Woo, Hyung-June; Dinner, Aaron R.; Roux, Benoît The Journal of Chemical Physics, Vol. 121, Issue 13 https://doi.org/10.1063/1.1784436	journal	October 2004
Computation of binding free energy with molecular dynamics and grand canonical Monte Carlo simulations Deng, Yuqing; Roux, Benoît The Journal of Chemical Physics, Vol. 128, Issue 11 https://doi.org/10.1063/1.2842080	journal	March 2008
The lag between the Hamiltonian and the system configuration in free energy perturbation calculations Pearlman, David A.; Kollman, Peter A. The Journal of Chemical Physics, Vol. 91, Issue 12 https://doi.org/10.1063/1.457251	journal	December 1989
Thermodynamic integration of the free energy along a reaction coordinate in Cartesian coordinates den Otter, W. K. The Journal of Chemical Physics, Vol. 112, Issue 17 https://doi.org/10.1063/1.481329	journal	May 2000
Scalable molecular dynamics on CPU and GPU architectures with NAMD Phillips, James C.; Hardy, David J.; Maia, Julio D. C. The Journal of Chemical Physics, Vol. 153, Issue 4 https://doi.org/10.1063/5.0014475	journal	July 2020
Random walk in orthogonal space to achieve efficient free-energy simulation of complex systems Zheng, L.; Chen, M.; Yang, W. Proceedings of the National Academy of Sciences, Vol. 105, Issue 51 https://doi.org/10.1073/pnas.0810631106	journal	December 2008
On achieving high accuracy and reliability in the calculation of relative protein-ligand binding affinities Wang, L.; Berne, B. J.; Friesner, R. A. Proceedings of the National Academy of Sciences, Vol. 109, Issue 6 https://doi.org/10.1073/pnas.1114017109	journal	January 2012
Exact reaction coordinates for flap opening in HIV-1 protease Wu, Shanshan; Li, Huiyu; Ma, Ao Proceedings of the National Academy of Sciences, Vol. 119, Issue 49 https://doi.org/10.1073/pnas.2214906119	journal	December 2022
OpenMM 7: Rapid development of high performance algorithms for molecular dynamics Eastman, Peter; Swails, Jason; Chodera, John D. PLOS Computational Biology, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pcbi.1005659	journal	July 2017
Enhanced Sampling Methods for Molecular Dynamics Simulations [Article v1.0] Hénin, Jérôme; Lelièvre, Tony; Shirts, Michael R. Living Journal of Computational Molecular Science, Vol. 4, Issue 1 https://doi.org/10.33011/livecoms.4.1.1583	journal	January 2022
Recent Developments in Free Energy Calculations for Drug Discovery King, Edward; Aitchison, Erick; Li, Han Frontiers in Molecular Biosciences, Vol. 8 https://doi.org/10.3389/fmolb.2021.712085	journal	August 2021

Similar Records

Studying the Collective Functional Response of a Receptor in Alchemical Ligand Binding Free Energy Simulations with Accelerated Solvation Layer Dynamics

Journal Article · Tue Apr 02 20:00:00 EDT 2024 · Journal of Chemical Theory and Computation · OSTI ID:2474889

Reduced Free Energy Perturbation/Hamiltonian Replica Exchange Molecular Dynamics Method with Unbiased Alchemical Thermodynamic Axis

Journal Article · Mon Sep 24 20:00:00 EDT 2018 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry · OSTI ID:1488538

Computing Relative Binding Affinity of Ligands to Receptor: An Effective Hybrid Single-Dual-Topology Free-Energy Perturbation Approach in NAMD

Journal Article · Tue Aug 13 20:00:00 EDT 2019 · Journal of Chemical Information and Modeling · OSTI ID:1570437

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Enhanced Configurational Sampling Approaches to Alchemical Ligand Binding Free Energy Simulations: Current Status and Challenges

Citation Formats

References (57)

Similar Records

Related Subjects