title: Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: molecular docking and 3D QSAR studies.
abstract: The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index analysis were conducted on a large series of selective inhibitors of trypanosomatid GAPDH. Four statistically significant models were obtained ( r2 > 0.90 and q2 > 0.70), indicating their predictive ability for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results. Molecular modeling studies provided further insight into the structural basis for selective inhibition of trypanosomatid GAPDH.
authors.affiliation: Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense 400, 13560-970, São Carlos-SP, Brazil.
authors.forename: Rafael V C
authors.initials: RV
authors.lastname: Guido
authors.forename: Glaucius
authors.initials: G
authors.lastname: Oliva
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Montanari
authors.forename: Adriano D
authors.initials: AD
authors.lastname: Andricopulo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008969:Molecular Sequence Data; D021281:Quantitative Structure-Activity Relationship; D017386:Sequence Homology, Amino Acid; D014345:Trypanosoma / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases