ArticleProceedings of the National Academy of Sciences of the United States of America2008
Calculation of protein-ligand binding free energy by using a polarizable potential.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 242 citations in OpenAlex.
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- Equilibrium and Nonequilibrium Ensemble Methods for Accurate, Precise and Reproducible Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2025Article
- Incorporating Neural Networks into the AMOEBA Polarizable Force Field.The journal of physical chemistry. B · 2024Article
- Accurate Host-Guest Binding Free Energies Using the AMOEBA Polarizable Force Field.Journal of chemical information and modeling · 2023Article
- Protein-Ligand Binding Free-Energy Calculations with ARROW─A Purely First-Principles Parameterized Polarizable Force Field.Journal of chemical theory and computation · 2022Article
- DyScore: A Boosting Scoring Method with Dynamic Properties for Identifying True Binders and Nonbinders in Structure-Based Drug Discovery.Journal of chemical information and modeling · 2022Article
- AMOEBA Force Field Trajectories Improve Predictions of Accurate pThe journal of physical chemistry. B · 2022Article
- Automation of AMOEBA polarizable force field for small molecules: Poltype 2.Journal of computational chemistry · 2022Article
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- Bayesian-Inference-Driven Model Parametrization and Model Selection for 2CLJQ Fluid Models.Journal of chemical information and modeling · 2022Article
- Computational study on the binding of Mango-II RNA aptamer and fluorogen using the polarizable force field AMOEBA.Frontiers in molecular biosciences · 2022Article
- Uncovering Differences in Hydration Free Energies and Structures for Model Compound Mimics of Charged Side Chains of Amino Acids.The journal of physical chemistry. B · 2021Article
- Design of intrinsically disordered proteins that undergo phase transitions with lower critical solution temperatures.APL materials · 2021Article
- Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation.Scientific reports · 2021Article
- AMOEBA binding free energies for the SAMPL7 TrimerTrip host-guest challenge.Journal of computer-aided molecular design · 2021Article
- Molecular dynamics free energy simulations of ATP:MgMolecular simulation · 2021Article
- Structure based design, stability study and synthesis of the dinitrophenylhydrazone derivative of the oxidation product of lanosterol as a potentialIn silico pharmacology · 2021Article
- Toward Automated Free Energy Calculation with Accelerated Enveloping Distribution Sampling (A-EDS).Journal of chemical information and modeling · 2020Article
- Alchemical Binding Free Energy Calculations in AMBER20: Advances and Best Practices for Drug Discovery.Journal of chemical information and modeling · 2020Article
47 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 1 country.
Funding
Abstract
The binding of charged ligands benzamidine and diazamidine to trypsin was investigated by using a polarizable potential energy function and explicit-water molecular dynamics simulations. The binding free energies were computed from the difference between the free energies of decoupling the ligand from water and protein environments. Both the absolute and the relative free energies from the perturbation simulations agree with experimental measurements to within 0.5 kcal.mol(-1). Comparison of free-energy components sampled from different thermodynamic paths indicates that electrostatics is the main driving force behind benzamidine recognition of trypsin. The contribution of electronic polarization to binding appears to be crucial. By computing the free-energy contribution caused by the polarization between the ligand and its surroundings, we found that polarization has the opposite effect in dissimilar environments. Although polarization favors ligand solvation in water, it weakens the protein-ligand attraction by screening the electrostatic interaction between trypsin and benzamidine. We also examined the relative binding free energies of a benzamidine analog diazamidine to trypsin. The changes in free energy on benzamidine-diazamidine substitution were tens of kilocalories in both water and trypsin environments; however, the change in the total binding free energy is <2 kcal.mol(-1) because of cancellation, consistent with the experimental results. Overall, our results suggest that the use of a polarizable force field, given adequate sampling, is capable of achieving chemical accuracy in molecular simulations of protein-ligand recognition.
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