Resumen

PEREZ, L.J  y  DIAZ DE ARCE, Heidy. OPTIMIZATION OF SCORING FUNCTION DOCKING FOR ANTIVIRAL DRUG DESIGN AGAINST CORONAVIRUS GENUS. Rev Salud Anim. [online]. 2008, vol.30, n.3, pp. 160-165. ISSN 0253-570X.

The development of a wide-spectrum antiviral drug against pathogenic coronavirus is nowadays a attractive prospect and may provide an effective first line of defense against emerging CoV-related diseases. The most attractive target for the design of anticoronaviral inhibitors is the main protease or 3CL^PRO. Ligand docking and screening algorithms are now frequently used in the drug-design process. The aim of this work based on a validation study of scoring functions is to find a consensus function or to select the scoring function that better predicts the orientation of the ligand in the pocket binding site, in order to perform a virtual screening in ligand databases, with a lower computational cost in the intent of finding a leader compound for antiviral drug against coronaviruses. For this purpose, the scoring functions were implemented within the Dock4.0 program suite and the 2ALV main protease three dimensional structures will be used. The protein structure was selected because it was crystallized with a non-peptidic ligand. The main protease coronavirus pocket including the catalytic dyad Cys145 His41 was obtained. The closer RSMD media values to 4.0 A^o were obtained using the contact score function from the rigid ligand dock method. This score function was selected as the best ranking tool for the search based on virtual screening of the potential candidate inhibitors of the important pathogen group belonging to the genus coronavirus.

Palabras clave : docking algorithms; scoring functions; rigid docking; flexible docking; main protease.