Covalent Docking to the Active Sites of Thiamine Diphosphate-Dependent Enzymes.

ABSTRACT: The search for novel low-molecular regulators using molecular docking continues to be crucial for addressing challenges in modern biomedical science. However, the current literature lacks examples of modeling covalent interactions between the ligands being docked and those already present within the proteins, such as enzyme cofactors. This study aims to improve the existing algorithms for modeling such interactions, exemplified by those in thiamine diphosphate (ThDP)-dependent enzymes. Structures containing adducts of ThDP with enzyme substrates or inhibitors are used as protein templates; the putative ligand models are prepared as (R)- or (S)-hydroxy derivatives. The Gnina framework with AD4 or Vinardo favors ligand conformations resembling those found in the protein templates and consist

SUBMITTER: Artiukhov AV 

PROVIDER: S-EPMC12655727 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature