A self-organizing algorithm for molecular alignment and pharmacophore development

Abstract: We present a method for simultaneous three-dimensional (3D) structure generation and pharmacophorebased alignment using a self-organizing algorithm called Stochastic Proximity Embedding (SPE). Current flexible molecular alignment methods either start from a single low-energy structure for each molecule and tweak bonds or torsion angles, or choose from multiple conformations of each molecule. Methods that generate structures and align them iteratively (e.g., genetic algorithms) are often slow. In earlier work, we used SPE to generate good-quality 3D conformations by iteratively adjusting pairwise distances between atoms based on a set of geometric rules, and showed that it samples conformational space better and runs faster than earlier programs. In this work, we run SPE on the entire ensemble of molecules to be aligned. Additional information about which atoms or groups of atoms in each molecule correspond to points in the pharmacophore can come from an automatically generate...

• Type: Journal
• Year: 2008
• Where: JCC
• Authors: Deepak Bandyopadhyay, Dimitris K. Agrafiotis
• Keywords: JCC 2008, Molecular Alignment, Pharmacophore, Stochastic Proximity