Docking of Covalent Ligands: Challenges and Approaches.

摘要: Covalent ligands have recently regained considerable attention in drug discovery. The rational design of such ligands, however, is still faced with particular challenges, mostly related to the fact that covalent bond formation a quantum mechanical phenomenon which cannot adequately be handled by force fields or empirical approaches typically used for noncovalent protein-ligand interactions. Although necessity chemical clear, they yet routinely applied on large data sets broader exploration binding modes docking calculations. On other hand, technical solutions performing calculations are available, but their scope normally quite limited. Scoring functions neglect contribution from completely. In this situation, question arises how approach and methods choose design.