ArticleMethods in molecular biology (Clifton, N.J.)2015
Site Identification by Ligand Competitive Saturation (SILCS) simulations for fragment-based drug design.
Article in Methods in molecular biology (Clifton, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Computer-Aided Drug Design for Type 2 Diabetes-Related Enzymes: SILCS-Based Fragment Mapping, Pharmacophore Modeling, and Virtual Screening.Journal of chemical information and modeling · 2026Article
- Arrhythmia risk predictions from molecular simulations of cardiac ion channel-drug interactions.Biophysical journal · 2026Article
- Boosting Drug Discovery: Expanding the Applicability of Fragment Dissolved Molecular Dynamics to Accelerate Binding Mode Elucidation.Journal of chemical information and modeling · 2025Article
- Prediction of TdP Arrhythmia Risk Through Molecular Simulations of Conformation-specific Drug Interactions with the hERG KbioRxiv : the preprint server for biology · 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
- CosolvKit: a Versatile Tool for Cosolvent MD Preparation and Analysis.Journal of chemical information and modeling · 2024Article
- Directional ΔJournal of chemical information and modeling · 2024Article
- Expanding FTMap for Fragment-Based Identification of Pharmacophore Regions in Ligand Binding Sites.Journal of chemical information and modeling · 2024Article
- Classification of likely functional class for ligand binding sites identified from fragment screening.Communications biology · 2024Article
- Preventing lipophilic aggregation in cosolvent molecular dynamics simulations with hydrophobic probes using Plumed Automatic Restraining Tool (PART).Journal of cheminformatics · 2024Article
- Structural and thermodynamic framework for PIEZO1 modulation by small molecules.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- FASTDock: A Pipeline for Allosteric Drug Discovery.Journal of chemical information and modeling · 2023Article
- Site Identification by Ligand Competitive Saturation-Biologics Approach for Structure-Based Protein Charge Prediction.Molecular pharmaceutics · 2023Article
- Computer-Aided Drug Design: An Update.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Nitro-benzylideneoxymorphone, a bifunctional mu and delta opioid receptor ligand with high mu opioid receptor efficacy.Frontiers in pharmacology · 2023Article
- Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations.Journal of chemical information and modeling · 2022Article
- hERG Blockade Prediction by Combining Site Identification by Ligand Competitive Saturation and Physicochemical Properties.Chemistry (Basel, Switzerland) · 2022Article
- Rapid and accurate estimation of protein-ligand relative binding affinities using site-identification by ligand competitive saturation.Chemical science · 2021Article
- Assessing hERG1 Blockade from Bayesian Machine-Learning-Optimized Site Identification by Ligand Competitive Saturation Simulations.Journal of chemical information and modeling · 2020Article
- Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Fragment-based drug design (FBDD) involves screening low molecular weight molecules ("fragments") that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind nonoverlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy.The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is "soaked" in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called "FragMaps" can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine "Grid Free Energies (GFEs)," which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities.
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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.