ArticlePLoS computational biology2015
Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Advances and Challenges in Milestoning Simulations for Drug-Target Kinetics.Journal of chemical theory and computation · 2024Article
- Prediction of Threonine-Tyrosine Kinase Receptor-Ligand Unbinding Kinetics with Multiscale Milestoning and Metadynamics.The journal of physical chemistry letters · 2024Article
- Predicting Biomolecular Binding Kinetics: A Review.Journal of chemical theory and computation · 2023Review
- 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
- Umbrella Sampling Simulations Measure Switch Peptide Binding and Hydrophobic Patch Opening Free Energies in Cardiac Troponin.Journal of chemical information and modeling · 2022Article
- Multiscale simulation-guided design of enzyme bioconjugates with enhanced catalysis.Chem catalysis · 2022Article
- Protein Flexibility and Dissociation Pathway Differentiation Can Explain Onset of Resistance Mutations in Kinases.Angewandte Chemie (International ed. in English) · 2022Article
- SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine.Journal of chemical information and modeling · 2022Article
- Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitors.Nature communications · 2022Article
- Challenges and frontiers of computational modelling of biomolecular recognition.QRB discovery · 2022Article
- New perspectives in cancer drug development: computational advances with an eye to design.RSC medicinal chemistry · 2021Review
- Reduced efficacy of a Src kinase inhibitor in crowded protein solution.Nature communications · 2021Article
- Atomistic Basis of Microtubule Dynamic Instability Assessed Via Multiscale Modeling.Annals of biomedical engineering · 2021Article
- Computational Modeling as a Tool to Investigate PPI: From Drug Design to Tissue Engineering.Frontiers in molecular biosciences · 2021Review
- Protein storytelling through physics.Science (New York, N.Y.) · 2020Review
- Value of Temporal Information When Analyzing Reaction Coordinates.Journal of chemical theory and computation · 2020Article
- Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein-Protein Association.Biomolecules · 2020Article
- Exploring the Reaction Mechanism of HIV Reverse Transcriptase with a Nucleotide Substrate.The journal of physical chemistry. B · 2020Article
- Encounter complexes and hidden poses of kinase-inhibitor binding on the free-energy landscape.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The kinetic rate constants of binding were estimated for four biochemically relevant molecular systems by a method that uses milestoning theory to combine Brownian dynamics simulations with more detailed molecular dynamics simulations. The rate constants found using this method agreed well with experimentally and theoretically obtained values. We predicted the association rate of a small charged molecule toward both a charged and an uncharged spherical receptor and verified the estimated value with Smoluchowski theory. We also calculated the kon rate constant for superoxide dismutase with its natural substrate, O2-, in a validation of a previous experiment using similar methods but with a number of important improvements. We also calculated the kon for a new system: the N-terminal domain of Troponin C with its natural substrate Ca2+. The kon calculated for the latter two systems closely resemble experimentally obtained values. This novel multiscale approach is computationally cheaper and more parallelizable when compared to other methods of similar accuracy. We anticipate that this methodology will be useful for predicting kinetic rate constants and for understanding the process of binding between a small molecule and a protein receptor.
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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.