title: PLS-DA - Docking Optimized Combined Energetic Terms (PLSDA-DOCET) protocol: a brief evaluation.
abstract: Docking studies have become popular approaches in drug design, where the binding energy of the ligand in the active site of the protein is estimated by a scoring function. Many promising techniques were developed to enhance the performance of scoring functions including the fusion of multiple scoring functions outcomes into a so-called consensus scoring function. Hereby, we evaluated the target oriented consensus technique using the energetic terms of several scoring functions. The approach was denoted PLSDA-DOCET. Optimization strategies for consensus energetic terms and scoring functions based on ROC metric were compared to classical rigid docking and to ligand-based similarity search methods comprising 2D fingerprints and ROCS. The ROCS results indicate large performance variations depending on the biological target. The AUC-based strategy of PLSDA-DOCET outperformed the other docking approaches regarding simple retrieval and scaffold-hopping. The superior performance of PLSDA-DOCET protocol relative to single and combined scoring functions was validated on an external test set. We found a relative low mean correlation of the ranks of the chemotypes retrieved by the PLSDA-DOCET protocol and all the other methods employed here.
authors: Department of Computational Chemistry, Institute of Chemistry of Romanian Academy, Timisoara, Mihai Viteazul Avenue, 24, 300223 Timisoara, Romania.
authors: Sorin
authors: S
authors: Avram
authors: Liliana M
authors: LM
authors: Pacureanu
authors: Edward
authors: E
authors: Seclaman
authors: Alina
authors: A
authors: Bora
authors: Ludovic
authors: L
authors: Kurunczi
mesh_terms: D000465:Algorithms; D020134:Catalytic Domain; D015195:Drug Design; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D011506:Proteins