ArticleJournal of chemical information and modeling2015
Mapping functional group free energy patterns at protein occluded sites: nuclear receptors and G-protein coupled receptors.
Article in Journal of chemical information and modeling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Uncovering hidden druggable sites: computational approaches to allosteric and cryptic pocket discovery-from molecular dynamics to AI.Journal of computer-aided molecular design · 2026Review
- Docking-score landscapes shape active-learning performance across Vina, Glide, and SILCS.Journal of computer-aided molecular design · 2026Article
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Computational Ligand-Binding Site Prediction.Advances in experimental medicine and biology · 2026Review
- GaSal-2: A Water-Soluble Antipseudomonal Agent Targeting the Extracellular Hemophore HasAp.ACS infectious diseases · 2025Article
- Potent and Selective Human Constitutive Androstane Receptor Activator DL5055 Facilitates Cyclophosphamide-Based Chemotherapies.Journal of medicinal chemistry · 2025Article
- Detection of Putative Ligand Dissociation Pathways in Proteins Using Site-Identification by Ligand Competitive Saturation.Journal of chemical information and modeling · 2025Article
- Modeling Ligand Binding Site Water Networks with Site Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities.Journal of chemical theory and computation · 2024Article
- Article
- Enhancing SILCS-MC via GPU Acceleration and Ligand Conformational Optimization with Genetic and Parallel Tempering Algorithms.The journal of physical chemistry. B · 2024Article
- Identifying and Assessing Putative Allosteric Sites and Modulators for CXCR4 Predicted through Network Modeling and Site Identification by Ligand Competitive Saturation.The journal of physical chemistry. B · 2024Article
- GPU-specific algorithms for improved solute sampling in grand canonical Monte Carlo simulations.Journal of computational chemistry · 2023Article
- Identification of a novel transport system in Borrelia burgdorferi that links the inner and outer membranes.Pathogens and disease · 2023Article
- Nitro-benzylideneoxymorphone, a bifunctional mu and delta opioid receptor ligand with high mu opioid receptor efficacy.Frontiers in pharmacology · 2023Article
- A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.International journal of molecular sciences · 2022Review
- In silico identification of a βProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Application of Site-Identification by Ligand Competitive Saturation in Computer-Aided Drug Design.New journal of chemistry = Nouveau journal de chimie · 2022Article
- Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Probe Confined Dynamic Mapping for G Protein-Coupled Receptor Allosteric Site Prediction.ACS central science · 2021Article
- AlphaFold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure, and Function.Journal of chemical information and modeling · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Occluded ligand-binding pockets (LBP) such as those found in nuclear receptors (NR) and G-protein coupled receptors (GPCR) represent a significant opportunity and challenge for computer-aided drug design. To determine free energies maps of functional groups of these LBPs, a Grand-Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) strategy is combined with the Site Identification by Ligand Competitive Saturation (SILCS) methodology. SILCS-GCMC/MD is shown to map functional group affinity patterns that recapitulate locations of functional groups across diverse classes of ligands in the LBPs of the androgen (AR) and peroxisome proliferator-activated-γ (PPARγ) NRs and the metabotropic glutamate (mGluR) and β2-adreneric (β2AR) GPCRs. Inclusion of protein flexibility identifies regions of the binding pockets not accessible in crystal conformations and allows for better quantitative estimates of relative ligand binding affinities in all the proteins tested. Differences in functional group requirements of the active and inactive states of the β2AR LBP were used in virtual screening to identify high efficacy agonists targeting β2AR in Airway Smooth Muscle (ASM) cells. Seven of the 15 selected ligands were found to effect ASM relaxation representing a 46% hit rate. Hence, the method will be of use for the rational design of ligands in the context of chemical biology and the development of therapeutic agents.
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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.