Web services as applications' integration tool: QikProp case study.

Web services are a new technology that enables to integrate applications running on different platforms by using primarily XML to enable communication among different computers over the Internet. Large number of applications was designed as stand alone systems before the concept of Web services was introduced and it is a challenge to integrate them into larger computational networks. A generally applicable method of wrapping stand alone applications into Web services was developed and is described.

Allosteric antagonist binding sites in class B GPCRs: corticotropin receptor 1.

The 41 amino acid neuropeptide, corticotropin-releasing factor (CRF) and its associated receptors CRF(1)-R and CRF(2)-R have been targeted for treating stress related disorders. Both CRF(1)-R and CRF(2)-R belong to the class B G-protein coupled receptors for which little information is known regarding the small molecule antagonist binding characteristics. However, it has been shown recently that different non-peptide allosteric ligands stabilize different receptor conformations for CRF(1)-R and hence an understanding of the ligand induced receptor conformational changes is important in the pharmacology of ligand binding.

Prediction of the 3D structure and dynamics of human DP G-protein coupled receptor bound to an agonist and an antagonist.

Prostanoids play important physiological roles in the cardiovascular and immune systems and in pain sensation in peripheral systems through their interactions with eight G-protein coupled receptors. These receptors are important drug targets, but development of subtype specific agonists and antagonists has been hampered by the lack of 3D structures for these receptors. We report here the 3D structure for the human DP G-protein coupled receptor (GPCR) predicted by the MembStruk computational method.

High affinity targets of protein kinase inhibitors have similar residues at the positions energetically important for binding.

Inhibition of protein kinase activity is a focus of intense drug discovery efforts in several therapeutic areas. Major challenges facing the field include understanding of the factors determining the selectivity of kinase inhibitors and the development of compounds with the desired selectivity profile. Here, we report the analysis of sequence variability among high and low affinity targets of eight different small molecule kinase inhibitors (BIRB796, Tarceva, NU6102, Gleevec, SB203580, balanol, H89, PP1).

Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase.

Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics.