FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects

Abstract

Background: Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making.

Pemanfaatan bioinformatika dalam bidang pertanian dan kesehatan (The utilization of bioinformatics in the field of agriculture and health)

“…Pustaka tersebut kemudian dapat menjadi acuan untuk eksperimen skrining obat secara in silico atau studi pemodelan terkait (Lagorce et al, 2008). Penggunaan piranti-piranti lunak daring tersebut banyak diarahkan untuk pengembangan obat dengue, avian influenza, dan kanker serviks (Wei et al, 2006;Lim et al, 2013;Bakri et al, 2014).…”

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“…AutoDock combines an empirical free energy force field with a Lamarckian genetic algorithm, providing fast prediction of bound conformations with predicted free energies of association. [39] Docking experiments were performed with AutoDock4, and all the molecules were docked with the target on the same pocket on which the natural molecules were docked [ Tables 6 and 7].…”

Les chimiothèques ciblant les interactions protéine-protéine

“…La construction d'un tel modèle a permis le dévelop-pement d'un logiciel librement accessible, PPI-HitProfiler (http:// www.cdithem.fr/getPPIHitProfiler.php), dont la fonction consiste à sélectionner, parmi les composés d'une chimiothèque, ceux ayant le plus fort potentiel pour moduler une interaction proté ine-proté ine. PPI-HitProfiler peut, en outre, être utilisé directement au sein de l'outil en ligne FAF-drugs2 (http://fafdrugs2.mti.univ-paris-diderot.fr) [38,39], qui permet plus globalement de filtrer toute chimiothèque selon de nombreux critères, notamment d'ADME-Tox (absorption, distribution, métabolisme, excrétion, toxicité). La validation de PPI-HitProfiler a été réalisée sur les données expérimentales de criblage de 11 cibles PPI (protein-protein interaction) différentes et un nombre cumulé de 500 000 molécules chimiques.…”