ArticleJournal of chemical theory and computation2020
Sampling Conformational Changes of Bound Ligands Using Nonequilibrium Candidate Monte Carlo and Molecular Dynamics.
Article in Journal of chemical theory and computation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Immunoinformatics-driven multi-epitope vaccine design as a promising strategy against multidrug-resistant pathogens: a comprehensive review.Folia microbiologica · 2026Review
- Benchmarking Docking Protocols on Predicting Alternative Binding Modes.Journal of chemical information and modeling · 2026Article
- An Automated Workflow for Diagnosing Sampling Issues Caused by Slow Torsional Motions in Molecular Simulations.Journal of chemical information and modeling · 2026Article
- Toward the Prediction of Binding Events in Very Flexible, Allosteric, Multidomain Proteins.Journal of chemical information and modeling · 2025Article
- Liquid-Liquid Phase Separation Associated with Intrinsically Disordered Proteins: Experimental and Computational Tools.Current protein & peptide science · 2025Review
- Predicting binding events in very flexible, allosteric, multi-domain proteins.bioRxiv : the preprint server for biology · 2024Article
- Reliability of AlphaFold2 Models in Virtual Drug Screening: A Focus on Selected Class A GPCRs.International journal of molecular sciences · 2024Article
- Virtual screening and molecular dynamics studies of novel small molecules targetingIn silico pharmacology · 2024Article
- Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity.Journal of chemical information and modeling · 2023Article
- WaterKit: Thermodynamic Profiling of Protein Hydration Sites.Journal of chemical theory and computation · 2023Article
- An overview of the SAMPL8 host-guest binding challenge.Journal of computer-aided molecular design · 2022Article
- Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.Journal of chemical theory and computation · 2022Article
- Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks [Article v0.1].Living journal of computational molecular science · 2022Article
- Enhancing water sampling of buried binding sites using nonequilibrium candidate Monte Carlo.Journal of computer-aided molecular design · 2021Article
- Reversibly Sampling Conformations and Binding Modes Using Molecular Darting.Journal of chemical theory and computation · 2021Article
- Best Practices for Alchemical Free Energy Calculations [Article v1.0].Living journal of computational molecular science · 2020Article
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Authors and funding
4 authors.
Funding
Abstract
Flexible ligands often have multiple binding modes or bound conformations that differ by rotation of a portion of the molecule around internal rotatable bonds. Knowledge of these binding modes is important for understanding the interactions stabilizing the ligand in the binding pocket, and other studies indicate it is important for calculating accurate binding affinities. In this work, we use a hybrid molecular dynamics (MD)/nonequilibrium candidate Monte Carlo (NCMC) method to sample the different binding modes of several flexible ligands and also to estimate the population distribution of the modes. The NCMC move proposal is divided into three parts. The flexible part of the ligand is alchemically turned off by decreasing the electrostatics and steric interactions gradually, followed by rotating the rotatable bond by a random angle and then slowly turning the ligand back on to its fully interacting state. The alchemical steps prior to and after the move proposal help the surrounding protein and water atoms in the binding pocket relax around the proposed ligand conformation and increase move acceptance rates. The protein-ligand system is propagated using classical MD in between the NCMC proposals. Using this MD/NCMC method, we were able to correctly reproduce the different binding modes of inhibitors binding to two kinase targets-c-Jun N-terminal kinase-1 and cyclin-dependent kinase 2-at a much lower computational cost compared to conventional MD and umbrella sampling. This method is available as a part of the BLUES software package.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.