We have developed a new tool for virtual database screening. This tool, referred to as the Generic Evolutionary Method for molecular DOCKing (GEMDOCK), combines an evolutionary approach and a new pharmacophore-based scoring function. The former integrates discrete and continuous global search strategies with local search strategies to speed up convergence. The latter simultaneously serves as th...

Nuclear receptors (NRs) constitute an important class of therapeutic targets. We evaluated the performance of 3D structure-based and ligand-based pharmacophore models in predicting the pharmacological profile of NRs ligands using the NRLiSt BDB database. We could generate selective pharmacophores for agonist and antagonist ligands and we found that the best performances were obtained by combini...

Pharmacophores can be defined in a number of ways [1, 2]. From a physical standpoint a pharmacophore is a collection of electronic and steric features of a molecule that allow it to exhibit activity against a given biological target. More specifically, a pharmacophore can be defined by a set of atoms and various geometric (distances, angles, torsions) relationships between them. The pharmacopho...

Objective: Uses molecular docking and pharmacophore modeling methods to examine the antimalarial activity of apigenin (API) on distinct kinds varieties P. falciparum (Pf) receptors. Methods: Using Autodock 4.0.1 ligandscout software, was conducted multiple types Pf receptors, including lactate dehydrogenase (Oxidoreductase), Enoyl-acyl carrier-protein Triose-phosphate (Isomerase), plasmepsin II...

The need to account for the dynamic behavior of a receptor has long been recognized as a complicating factor in computational drug design. The use of a single, rigid protein structure—usually from a high-quality X-ray crystal structure— still is the standard in most applications (Zheng and Kyle, 1997; Walters et al., 1998). The choice to use a single protein structure is usually based on speed....

The mammalian olfactory system comprises a large family of G protein-coupled receptors (GPCRs) to detect and discriminate numerous volatile ligands. More than 350 human genes encode functional olfactory receptors (ORs) that belong to the class A (rhodopsin-like) GPCR family. Owing to difficulties with functional OR expression in heterologous systems, only a few humanORs have been characterized ...

Abstract: Second extracellular loop (ecl2) of the dopamine (DA) D2 receptor is an essential part of the binding pocket of dopaminergic ligands. To form a part of the ligand-binding surface, it has to fold down into the transmembrane domain of the DA receptor. The current study describes the modeling of the D2 DA receptor ecl2 and its interactions with arylpiperazine ligands. In order to model t...

The elaboration of a pharmacophore model for the delta opioid receptor selective ligand JOM-13 (Tyr-c[D-Cys-Phe-D-Pen]OH) and the parallel, independent development of a structural model of the delta receptor are summarized. Although the backbone conformation of JOM-13's tripeptide cycle is well defined, considerable conformational lability is evident in the Tyr(1) residue and in the Phe(3) side...

Virtual screening (VS) overcomes the limitations of traditional high-throughput screening (HTS) by applying computer-based methods in drug discovery. VS takes advantage of fast algorithms to filter chemical space and successfully select potential drug candidates. A key aspect in structure-based VS is the sampling of ligand-receptor conformations and the evaluation of these poses to predict near...