ArticleThe journal of physical chemistry. B2011
Elucidating the energetics of entropically driven protein-ligand association: calculations of absolute binding free energy and entropy.
Article in The journal of physical chemistry. B, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Binding of Anthracyclines Within DNA-Topoisomerase ΙΙ Cleavage Complexes: Thermodynamics and Interactions.Journal of chemical information and modeling · 2026Article
- Toward Reconciling the Standard Binding Free Energy of Lenacapavir to HIV-1 Capsid with Experiment: Thermodynamic Effects of Solvent Buffer and Ligand Reorganization.The journal of physical chemistry. B · 2026Article
- The Role of Medium Polarity in the Efficiency of Albumin Binding with Hydrophobic Ligands: Experimental Studies and a Molecular Dynamics Investigation.International journal of molecular sciences · 2024Article
- Computational Analysis of Heat Capacity Effects in Protein-Ligand Binding.Journal of chemical theory and computation · 2024Article
- Design of Inhibitors That Target the Menin-Mixed-Lineage Leukemia Interaction.Computation (Basel, Switzerland) · 2024Article
- Evolutionary divergence in the conformational landscapes of tyrosine vs serine/threonine kinases.eLife · 2022Article
- Structure-based virtual screening workflow to identify antivirals targeting HIV-1 capsid.Journal of computer-aided molecular design · 2022Article
- Molecular Docking Simulation Studies Identifies Potential Natural Product Derived-Antiwolbachial Compounds as Filaricides against Onchocerciasis.Biomedicines · 2021Article
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- A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor ofBiomolecules · 2021Article
- Cheminformatics-Based Identification of Potential Novel Anti-SARS-CoV-2 Natural Compounds of African Origin.Molecules (Basel, Switzerland) · 2021Article
- Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.Chemical reviews · 2020Review
- Combining Alchemical Transformation with a Physical Pathway to Accelerate Absolute Binding Free Energy Calculations of Charged Ligands to Enclosed Binding Sites.Journal of chemical theory and computation · 2020Article
- Absolute Protein Binding Free Energy Simulations for Ligands with Multiple Poses, a Thermodynamic Path That Avoids Exhaustive Enumeration of the Poses.Journal of computational chemistry · 2020Article
- Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments.Molecules (Basel, Switzerland) · 2019Article
- Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands.Physical chemistry chemical physics : PCCP · 2018Article
- Resolving the Ligand-Binding Specificity in c-MYC G-Quadruplex DNA: Absolute Binding Free Energy Calculations and SPR Experiment.The journal of physical chemistry. B · 2017Article
- A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain.The Journal of biological chemistry · 2016Article
- Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015.Journal of computer-aided molecular design · 2016Article
- Binding Energy Distribution Analysis Method: Hamiltonian Replica Exchange with Torsional Flattening for Binding Mode Prediction and Binding Free Energy Estimation.Journal of chemical theory and computation · 2016Article
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Authors and funding
4 authors.
Funding
Abstract
The binding of proteins and ligands is generally associated with the loss of translational, rotational, and conformational entropy. In many cases, however, the net entropy change due to binding is positive. To develop a deeper understanding of the energetics of entropically driven protein-ligand binding, we calculated the absolute binding free energies and binding entropies for two HIV-1 protease inhibitors Nelfinavir and Amprenavir using the double-decoupling method with molecular dynamics simulations in explicit solvent. For both ligands, the calculated absolute binding free energies are in general agreement with experiments. The statistical error in the computed ΔG(bind) due to convergence problem is estimated to be ≥2 kcal/mol. The decomposition of free energies indicates that, although the binding of Nelfinavir is driven by nonpolar interaction, Amprenavir binding benefits from both nonpolar and electrostatic interactions. The calculated absolute binding entropies show that (1) Nelfinavir binding is driven by large entropy change and (2) the entropy of Amprenavir binding is much less favorable compared with that of Nelfinavir. Both results are consistent with experiments. To obtain qualitative insights into the entropic effects, we decomposed the absolute binding entropy into different contributions based on the temperature dependence of free energies along different legs of the thermodynamic pathway. The results suggest that the favorable entropic contribution to binding is dominated by the ligand desolvation entropy. The entropy gain due to solvent release from binding site appears to be more than offset by the reduction of rotational and vibrational entropies upon binding.
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