Computational fragment-based binding site identification by ligand competitive saturation.

ABSTRACT: Fragment-based drug discovery using NMR and x-ray crystallographic methods has proven utility but also non-trivial time, materials, and labor costs. Current computational fragment-based approaches circumvent these issues but suffer from limited representations of protein flexibility and solvation effects, leading to difficulties with rigorous ranking of fragment affinities. To overcome these limitations we describe an explicit solvent all-atom molecular dynamics methodology (SILCS: Site Identification by Ligand Competitive Saturation) that uses small aliphatic and aromatic molecules plus water molecules to map the affinity pattern of a protein for hydrophobic groups, aromatic groups, hydrogen bond donors, and hydrogen bond acceptors. By simultaneously incorporating ligands representative o

SUBMITTER: Guvench O 

PROVIDER: S-EPMC2700966 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature