Conformer Generation for Structure-Based Drug Design: How Many and How Good?

ABSTRACT: Conformer generation, the assignment of realistic 3D coordinates to a small molecule, is fundamental to structure-based drug design. Conformational ensembles are required for rigid-body matching algorithms, such as shape-based or pharmacophore approaches, and even methods that treat the ligand flexibly, such as docking, are dependent on the quality of the provided conformations due to not sampling all degrees of freedom (e.g., only sampling torsions). Here, we empirically elucidate some general principles about the size, diversity, and quality of the conformational ensembles needed to get the best performance in common structure-based drug discovery tasks. In many cases, our findings may parallel "common knowledge" well-known to practitioners of the field. Nonetheless, we feel that it is v

SUBMITTER: McNutt AT 

PROVIDER: S-EPMC10647020 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature