Quantum Mechanical Assessment of Protein-Ligand Hydrogen Bond Strength Patterns: Insights from Semiempirical Tight-Binding and Local Vibrational Mode Theory.

ABSTRACT: Hydrogen bonds (HB)s are the most abundant motifs in biological systems. They play a key role in determining protein-ligand binding affinity and selectivity. We designed two pharmaceutically beneficial HB databases, database A including ca. 12,000 protein-ligand complexes with ca. 22,000 HBs and their geometries, and database B including ca. 400 protein-ligand complexes with ca. 2200 HBs, their geometries, and bond strengths determined via our local vibrational mode analysis. We identified seven major HB patterns, which can be utilized as a de novo QSAR model to predict the binding affinity for a specific protein-ligand complex. Glycine was reported as the most abundant amino acid residue in both donor and acceptor profiles, and N-H⋯O was the most frequent HB type found in database A. HBs

SUBMITTER: Madushanka A 

PROVIDER: S-EPMC10094336 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature