Assessing the geometric diversity of cytochrome P450 ligand conformers by hierarchical clustering with a stop criterion.
An algorithm is presented, which exhibits a computed number of rigid conformers of an input small molecule, covering the geometric diversity in the conformational space, with minimal structural redundancy. The algorithm calls a conformer generator, then performs an agglomerative hierarchical clustering with the modified clustering gain as the stop criterion. The number of classes is computed without an arbitrary parameter. A representative conformer is selected in each class, and nonrepresentative conformers are discarded. For illustration, the algorithm has been applied on a database containing 70 ligands of the cytochrome CYP 3A4, showing that the structural flexibility of each ligand is indeed handled via a small number of its representative conformers. The method is valid for all small molecules.
Meslamani
Jamel Eddine
JE
CEA/DSV/iBiTec-S/SB2SM (CNRS URA 2096), Gif-sur-Yvette, France.
André
François
F
Petitjean
Michel
M
D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008968:Molecular Conformation
D008024:Ligands; D003577:Cytochrome P-450 Enzyme System