S4MPLE—Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking

作者: Laurent Hoffer , Camelia Chira , Gilles Marcou , Alexandre Varnek , Dragos Horvath

DOI: 10.3390/MOLECULES20058997

关键词: Force field (chemistry)AlgorithmDocking (molecular)Computer scienceGenetic algorithmSearching the conformational space for dockingBenchmarkingConformational samplingProtein ligandComputational chemistry

摘要: This paper describes the development of unified conformational sampling and docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The main novelty in S4MPLE is dealing with intra- intermolecular degrees freedom (DoF). While classically programs are either designed folding or docking, transcends this artificial specialization. It supports folding, a flexible ligand into site simultaneous several ligands. trick behind it formal assimilation inter-molecular to intra-molecular DoF associated putative contact axes. implemented within genetic operators powering Lamarckian Genetic Algorithm (GA). Further includes differentiable interaction fingerprints control population diversity, fitting simple continuum solvent model favorable bonus terms AMBER/GAFF force field. Novel applications—docking fragment-like compounds, multiple ligands, including free crystallographic waters—were published elsewhere. discusses: (a) methodology, (b) set-up field energy functions (c) their validation classical redocking tests. More than 80% success was achieved (RMSD top-ranked pose < 2.0 A).

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