SENSAAS-Flex: a joint optimization approach for aligning 3D shapes and exploring the molecular conformation space - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Bioinformatics Année : 2024

SENSAAS-Flex: a joint optimization approach for aligning 3D shapes and exploring the molecular conformation space

Résumé

Popular shape-based alignment methods handle molecular flexibility by utilizing conformational ensembles to select the most fitted conformer. However, the initial conformer library generation step is computationally intensive and limiting to the overall alignment process. In this work, we describe a method to perform flexible alignment of two molecular shapes by optimizing the 3D conformation. SENSAAS-Flex, an add-on to the SENSAAS tool, is able to proceed from a limited set of initial conformers through an iterative process where additional conformational optimizations are made at the substructure level and constrained by the target shape. In self- and cross-alignment experiments, SENSAAS-Flex is able to reproduce the crystal structure geometry of ligands of the AstraZeneca Molecule Overlay Test set and PDBbind refined dataset. Our study shows that the point-based representation of molecular surfaces is appropriate in terms of shape constraint to sample the conformational space and perform flexible molecular alignments. Availability and implementation The documentation and source code are available at https://chemoinfo.ipmc.cnrs.fr/Sensaas-flex/sensaas-flex-main.tar.gz

Dates et versions

hal-04513312 , version 1 (20-03-2024)

Identifiants

Citer

Hamza Biyuzan, Mohamed-Akram Masrour, Lucas Grandmougin, Frédéric Payan, Dominique Douguet. SENSAAS-Flex: a joint optimization approach for aligning 3D shapes and exploring the molecular conformation space. Bioinformatics, 2024, 40 (3), ⟨10.1093/bioinformatics/btae105⟩. ⟨hal-04513312⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More