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Ligand-Binding-Site Structure Refinement Using Molecular Dynamics with Restraints Derived from Predicted Binding Site Templates
journal contribution
posted on 2019-10-14, 15:33 authored by Hugo Guterres, Hui Sun Lee, Wonpil ImAccurate modeling of ligand-binding-site
structures plays a critical
role in structure-based virtual screening. However, the structures
of the ligand-binding site in most predicted protein models are generally
of low quality and need refinements. In this work, we present a ligand-binding-site
structure refinement protocol using molecular dynamics simulation
with restraints derived from predicted binding site templates. Our
benchmark validation shows great performance for 40 diverse sets of
proteins from the Astex list. The ligand-binding sites on modeled
protein structures are consistently refined using our method with
an average Cα RMSD improvement of 0.90 Å. Comparison of
ligand binding modes from ligand docking to initial unrefined and
refined structures shows an average of 1.97 Å RMSD improvement
in the refined structures. These results demonstrate a promising new
method of structure refinement for protein ligand-binding-site structures.
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1.97 Å RMSD improvementligand-binding-site structure refinement protocolstructure refinementligand-binding sitebenchmark validation0.90 Å. Comparisonligand dockingMolecular Dynamicsprotein ligand-binding-site structuresligand-binding sitesAstex listRestraints DerivedLigand-Binding-Site Structure Refinementprotein structuresneed refinementsdynamics simulationligand-binding-site structuresprotein modelsC α RMSD improvementligand binding modesPredicted Binding Site Templatesbinding site templates
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