BACKGROUND Protein-based pharmacophore models are enriched with the information of potential interactions between ligands and the protein target. We have shown in a previous study that protein-based pharmacophore models can be applied for ligand pose prediction and pose ranking. In this publication, we present a new pharmacophore-based docking program PharmDock that combines pose sampling and r...

Activation of the peroxisome proliferator-activated receptor γ (PPARγ) is important for the treatment of type 2 diabetes and obesity through the regulation of glucose metabolism and fatty acid accumulation. Hence, the discovery of novel PPARγ agonists is necessary to overcome these diseases. In this study, a newly developed approach, multi-conformation dynamic pharmacophore modeling (MCDPM), wa...

Inhibition of chymase is likely to divulge therapeutic ways for the treatment of cardiovascular diseases, and fibrotic disorders. To find novel and potent chymase inhibitors and to provide a new idea for drug design, we used both ligand-based and structure-based methods to perform the virtual screening(VS) of commercially available databases. Different pharmacophore models generated from variou...

Pharmacophore modelling-based virtual screening of compound is a ligand-based approach and is useful when the 3D structure of target is not available but a few known active compounds are known. Pharmacophore mapping studies were undertaken for a set of 50 N(3)-phenylpyrazinones possessing Corticotropin-releasing Factor 1 (CRF 1) antagonistic activity. Six point pharmacophores with two hydrogen ...

Cannabinoid receptors (CB) are G-protein coupled receptors involved in many physiological processes, like learning, appetite, nociception and others. Two subtypes (termed CB1 and CB2) are involved in slightly different processes [1]. Thus, it is important to gain more insight into the the cannabinoid receptor system and the potential effects of cannabinoid therapeutics. By combining [2] 3D-QSAR...

Following major advances in the field of medicinal chemistry, novel drugs can now be designed systematically, instead of relying on old trial and error approaches. Current drug design strategies can be classified as being either ligand- or structure-based depending on the design process. In this paper, by describing the search for an ATP synthase inhibitor, we review two frequently used approac...

Purely structure-based pharmacophores (SBPs) are an alternative method to ligand-based approaches and have the advantage of describing the entire interaction capability of a binding pocket. Here, we present the development of SBPs for topoisomerase I, an anticancer target with an unusual ligand binding pocket consisting of protein and DNA atoms. Different approaches to cluster and select pharma...

We present the first receptor-based pharmacophore model for HIV-1 integrase. The development of "dynamic" pharmacophore models is a new method that accounts for the inherent flexibility of the active site and aims to reduce the entropic penalties associated with binding a ligand. Furthermore, this new drug discovery method overcomes the limitation of an incomplete crystal structure of the targe...

The role of activity cliffs in drug discovery projects is certainly two-edged: on the one hand, they often lead to the failure of QSAR modeling techniques; on the other, they are highly valuable for identifying key aspects of SARs. In the presence of activity cliffs the results of purely ligand-based QSAR approaches often remain puzzling, and the resulting models have limited predictive power. ...