Fragment and torsion biasing algorithms for construction of small organic molecules in proteins using DOCK.

ABSTRACT: The computational construction of small organic molecules (de novo design), directly in a protein binding site, is an effective means for generating novel ligands tailored to fit the pocket environment. In this work, we present two new methods, which aim to improve de novo design outcomes using (1) biasing algorithms to prioritize selection and/or acceptance of fragments and torsions during growth, and (2) parallel-based clustering and pruning algorithms to remove duplicate molecules as candidate fragment are added. Large-scale testing encompassing thousands of simulations were employed to interrogate the methods in terms of multiple metrics which include numbers of duplicate molecules generated, pairwise-similarity, focused library reconstruction rates, fragment and torsion frequencies, f

SUBMITTER: Bickel JD 

PROVIDER: S-EPMC11588537 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature