title: MIND-BEST: Web server for drugs and target discovery; design, synthesis, and assay of MAO-B inhibitors and theoretical-experimental study of G3PDH protein from Trichomonas gallinae.
abstract: Many drugs with very different affinity to a large number of receptors are described. Thus, in this work, we selected drug-target pairs (DTPs/nDTPs) of drugs with high affinity/nonaffinity for different targets. Quantitative structure-activity relationship (QSAR) models become a very useful tool in this context because they substantially reduce time and resource-consuming experiments. Unfortunately, most QSAR models predict activity against only one protein target and/or they have not been implemented on a public Web server yet, freely available online to the scientific community. To solve this problem, we developed a multitarget QSAR (mt-QSAR) classifier combining the MARCH-INSIDE software for the calculation of the structural parameters of drug and target with the linear discriminant analysis (LDA) method in order to seek the best model. The accuracy of the best LDA model was 94.4% (3,859/4,086 cases) for training and 94.9% (1,909/2,012 cases) for the external validation series. In addition, we implemented the model into the Web portal Bio-AIMS as an online server entitled MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (MIND-BEST), located at http://miaja.tic.udc.es/Bio-AIMS/MIND-BEST.php . This online tool is based on PHP/HTML/Python and MARCH-INSIDE routines. Finally, we illustrated two practical uses of this server with two different experiments. In experiment 1, we report for the first time a MIND-BEST prediction, synthesis, characterization, and MAO-A and MAO-B pharmacological assay of eight rasagiline derivatives, promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, MASCOT search, 3D structure modeling with LOMETS, and MIND-BEST prediction for different peptides as new protein of the found in the proteome of the bird parasite Trichomonas gallinae, which is promising for antiparasite drug targets discovery.
authors.affiliation: Department of Microbiology and Parasitology, University of Santiago de Compostela, Spain. gonzalezdiazh@yahoo.es
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
authors.forename: Francisco
authors.initials: F
authors.lastname: Prado-Prado
authors.forename: Xerardo
authors.initials: X
authors.lastname: García-Mera
authors.forename: Nerea
authors.initials: N
authors.lastname: Alonso
authors.forename: Paula
authors.initials: P
authors.lastname: Abeijón
authors.forename: Olga
authors.initials: O
authors.lastname: Caamaño
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Cristian R
authors.initials: CR
authors.lastname: Munteanu
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pazos
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Dea-Ayuela
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Gómez-Muñoz
authors.forename: M Magdalena
authors.initials: MM
authors.lastname: Garijo
authors.forename: José
authors.initials: J
authors.lastname: Sansano
authors.forename: Florencio M
authors.initials: FM
authors.lastname: Ubeira
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology; D010856:Columbidae / Q000382:microbiology; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005954:Glucosephosphate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry; D020407:Internet; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D014244:Trichomonas / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology
chemical_list: D000977:Antiparasitic Agents; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D010455:Peptides; D015800:Protozoan Proteins; C031967:rasagiline; D005954:Glucosephosphate Dehydrogenase; D008995:Monoamine Oxidase