FLUFF-BALL, A Template-Based Grid-Independent Superposition and QSAR Technique:  Validation Using a Benchmark Steroid Data Set

• Published in: Journal of Chemical Information and Computer Sciences Vol. 43; no. 6; pp. 1780 - 1793
• Main Authors: Korhonen, Samuli-Petrus, Tuppurainen, Kari, Laatikainen, Reino, Peräkylä, Mikael
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.11.2003
• Subjects: Algorithms; Chemical Phenomena; Chemistry, Physical; Computational Biology; Databases as Topic; Gene Library; Ligands; Models, Molecular; Quantitative Structure-Activity Relationship; Reproducibility of Results; Software; Steroids - chemistry; Templates, Genetic
• ISSN: 0095-2338; 1549-960X
• DOI: 10.1021/ci034027o

The Flexible Ligand Unified Force Field (FLUFF) is a molecular mechanistic superposition algorithm utilizing a template structure, on top of which the ligand(s) are superimposed. FLUFF enables a flexible semiautomatic superimposition in which the ligand and the template are allowed to seek the best common conformation, which can then be used to predict the biological activity by Boundless Adaptive Localized Ligand (BALL). In BALL, the similarity of the electrostatic and van der Waals volumes of the template and ligand is evaluated using the template-based coordinate system which makes the FLUFF-BALL invariant as to the rotations and translations of the global coordinate system. When tested using the CBG (corticosteroid binding globulin) affinities of 31 benchmark steroids, the FLUFF-BALL technique produced results comparable to standard 3D-QSAR methods. Supplementary test calculations were performed with five additional data sets. Due to its high level of automation and high throughput, the FLUFF-BALL is highly suitable for use in drug design and in scanning of large molecular libraries.