ArticleJournal of chemical information and modeling2012
Application of binding free energy calculations to prediction of binding modes and affinities of MDM2 and MDMX inhibitors.
Article in Journal of chemical information and modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 51 citations in OpenAlex.
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- Synthesis, molecular docking, and binding Gibbs free energy calculation of β-nitrostyrene derivatives: Potential inhibitors of SARS-CoV-2 3CL protease.Journal of molecular structure · 2023Article
- Detailed Experimental and In Silico Investigation of Indomethacin Binding with Human Serum Albumin Considering Primary and Secondary Binding Sites.Molecules (Basel, Switzerland) · 2023Article
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- Molecular docking of DS-3032B, a mouse double minute 2 enzyme antagonist with potential for oncology treatment development.World journal of clinical oncology · 2022Article
- Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis.Frontiers in pharmacology · 2022Article
- Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data.Biomolecules · 2021Article
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- Absolute Binding Free Energy Calculations for Highly Flexible Protein MDM2 and Its Inhibitors.International journal of molecular sciences · 2020Article
- Spectroscopic and Molecular Docking Investigation on the Noncovalent Interaction of Lysozyme with Saffron Constituent "Safranal".ACS omega · 2020Article
- Improving Protein-Ligand Docking Results with High-Throughput Molecular Dynamics Simulations.Journal of chemical information and modeling · 2020Article
- Molecular Docking: Shifting Paradigms in Drug Discovery.International journal of molecular sciences · 2019Review
- CHARMM-GUI PDB manipulator for advanced modeling and simulations of proteins containing nonstandard residues.Advances in protein chemistry and structural biology · 2014Review
- CHARMM-GUI Ligand Binder for absolute binding free energy calculations and its application.Journal of chemical information and modeling · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Molecular docking is widely used to obtain binding modes and binding affinities of a molecule to a given target protein. Despite considerable efforts, however, prediction of both properties by docking remains challenging mainly due to protein's structural flexibility and inaccuracy of scoring functions. Here, an integrated approach has been developed to improve the accuracy of binding mode and affinity prediction and tested for small molecule MDM2 and MDMX antagonists. In this approach, initial candidate models selected from docking are subjected to equilibration MD simulations to further filter the models. Free energy perturbation molecular dynamics (FEP/MD) simulations are then applied to the filtered ligand models to enhance the ability in predicting the near-native ligand conformation. The calculated binding free energies for MDM2 complexes are overestimated compared to experimental measurements mainly due to the difficulties in sampling highly flexible apo-MDM2. Nonetheless, the FEP/MD binding free energy calculations are more promising for discriminating binders from nonbinders than docking scores. In particular, the comparison between the MDM2 and MDMX results suggests that apo-MDMX has lower flexibility than apo-MDM2. In addition, the FEP/MD calculations provide detailed information on the different energetic contributions to ligand binding, leading to a better understanding of the sensitivity and specificity of protein-ligand interactions.
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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.