ArticleThe journal of physical chemistry letters2016
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.
Article in The journal of physical chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed.
- Hierarchical multi-timescale structural dynamics of the disordered N-terminal of p53.Nature communications · 2026Article
- Reducing weighted ensemble variance with optimal trajectory management.The Journal of chemical physics · 2026Article
- Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly.Journal of chemical theory and computation · 2025Article
- A Computational Perspective to Intermolecular Interactions and the Role of the Solvent on Regulating Protein Properties.Chemical reviews · 2025Review
- Ligand Gaussian Accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.Journal of chemical theory and computation · 2024Article
- Protein Retrieval via Integrative Molecular Ensembles (PRIME) through Extended Similarity Indices.Journal of chemical theory and computation · 2024Article
- Revisiting Textbook Azide-Clock Reactions: A "Propeller-Crawling" Mechanism Explains Differences in Rates.Journal of the American Chemical Society · 2024Article
- Ligand Gaussian accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.bioRxiv : the preprint server for biology · 2024Article
- Effects of altered backbone composition on the folding kinetics and mechanism of an ultrafast-folding protein.Chemical science · 2024Article
- Roles of Accelerated Molecular Dynamics Simulations in Predictions of Binding Kinetic Parameters.Mini reviews in medicinal chemistry · 2024Review
- LPATH: A Semiautomated Python Tool for Clustering Molecular Pathways.Journal of chemical information and modeling · 2023Article
- Markov State Model of Solvent Features Reveals Water Dynamics in Protein-Peptide Binding.The journal of physical chemistry. B · 2023Article
- Machine learning methods for developments of binding kinetic models in predicting protein-ligand dissociation rate constants.Smart molecules : open access · 2023Article
- LPATH: A semi-automated Python tool for clustering molecular pathways.bioRxiv : the preprint server for biology · 2023Article
- Binding-and-Folding Recognition of an Intrinsically Disordered Protein Using Online Learning Molecular Dynamics.Journal of chemical theory and computation · 2023Article
- Predicting Biomolecular Binding Kinetics: A Review.Journal of chemical theory and computation · 2023Review
- Structure Determination of Challenging Protein-Peptide Complexes Combining NMR Chemical Shift Data and Molecular Dynamics Simulations.Journal of chemical information and modeling · 2023Article
- Quality over quantity: Sampling high probability rare events with the weighted ensemble algorithm.Journal of computational chemistry · 2023Article
- Computational approaches for the design of modulators targeting protein-protein interactions.Expert opinion on drug discovery · 2023Review
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
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Authors and funding
6 authors.
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Abstract
The characterization of protein binding processes - with all of the key conformational changes - has been a grand challenge in the field of biophysics. Here, we have used the weighted ensemble path sampling strategy to orchestrate molecular dynamics simulations, yielding atomistic views of protein-peptide binding pathways involving the MDM2 oncoprotein and an intrinsically disordered p53 peptide. A total of 182 independent, continuous binding pathways were generated, yielding a kon that is in good agreement with experiment. These pathways were generated in 15 days using 3500 cores of a supercomputer, substantially faster than would be possible with "brute force" simulations. Many of these pathways involve the anchoring of p53 residue F19 into the MDM2 binding cleft when forming the metastable encounter complex, indicating that F19 may be a kinetically important residue. Our study demonstrates that it is now practical to generate pathways and calculate rate constants for protein binding processes using atomistic simulation on typical computing resources.
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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.