The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a structural model of AT1R was built making use of the growing set of crystal structu...

The HIV-1causes life-threatening infection by establishing essential biochemical interactions via its IN protein with human host LEDGF/p75 protein. The crystal structure availability of LEDEF–HIV-IN complex provide essential roadmap for designing small drug-like molecule to perturb pathogen-host proteins interaction. We adopted the in-silico drug discovery approaches and scanned the TIMBAL data...

MOTIVATION Automatic procedures to obtain pharmacophore models from experimentally determined macromolecular complexes can help in the drug discovery process, especially when protein-protein recognition plays an important biological role. RESULTS The GRID-based pharmacophore model (GBPM) is a fully objective method for defining most relevant interaction areas in complexes deriving pharmacopho...

N-Myristoyl transferase is an essential enzyme for fungal growth and survival. The continuous interest in the development of new antifungal agents prompted recent interest in developing new potent inhibitors of fungal N-myristoyl transferase. In this context, we combined pharmacophore and QSAR modeling to explore the structural requirements for potent N-myristoyl transferase inhibitors employin...

the urgent need of neuraminidase inhibitors (ni) has provided an impetus for understanding the structure requisite at molecular level. our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. the main objective of present study is to develop selective ni, with least toxicity and dru...

4D quantitative structure-activity relationship (QSAR) and 3D pharmacophore models were built and investigated for cytotoxicity using a training set of 25 lamellarins against human hormone dependent T47D breast cancer cells. Receptor-independent (RI) 4D QSAR models were first constructed from the exploration of eight possible receptor-binding alignments for the entire training set. Since the tr...

In the present study we have investigated whether pharmacophore models may account for the activity and selectivity of the known cyclooxygenase-2 (COX-2) selective inhibitors of the phenylsulfonyl tricyclic series, i.e., Celecoxib (1) and Rofecoxib (3), and whether transferring this structural information onto the frame of a nonsteroidal antiinflammatory drug (NSAID), known to tightly bind the ...

Gamma-secretase is a trans-membrane aspartyl protease that consists of four subunits, namely Anterior Pharynx Defective Phenotype (APH-1), Presenilin (PSEN), Nicastrin (Nct) and Presenilin 2 Enhancer (PEN2). Presenilin is identified as the catalytic core of gamma-secretase with the two aspartyl residues at the catalytic site. Gamma-secretase is involved in the ultimate step in the processing of...

The pregnane X receptor (PXR) is involved in transcriptional regulation of multiple cytochromes P450 and multidrug resistance-associated protein (MDR1), which encodes for the drug transporter P-glycoprotein. Crystal structure analyses suggest that the ligand binding domain is highly hydrophobic and flexible, allowing molecules of differing sizes to bind in multiple orientations. Using literatur...

Allosteric inhibition of protein tyrosine phosphatase 1B (PTP1B), has paved a new path to design specific inhibitors for PTP1B, which is an important drug target for the treatment of type II diabetes and obesity. The PTP1B1-282-allosteric inhibitor complex crystal structure lacks alpha7 (287-298) and moreover there is no available 3D structure of PTP1B1-298 in open form. As the interaction betw...