Current Pharmaceutical Design - Volume 12, Issue 17, 2006

The very foundations of drug discovery research are being rapidly transformed by high throughput systems, automated assays, robotics and advanced computational applications in medicinal chemistry. Costs are dropping, the time to complete a cycle of discovery and compound characterization is lessening, and all the while the ability to assess a compound's possible therapeutic role is improving. Indeed, the driv Read More

The identification of novel drug targets from genomic data involves the large-scale analysis of many protein sequences. Methods for automated structure and function prediction are an essential tool for this purpose. In this review we concentrate on the recent developments in the field of protein structure prediction and how these can be used to gain hints about the function of proteins. The current state-of-the-art is highli Read More

In the past few years macromolecular crystallography has become a standard technique used by many pharmaceutical and biotechnology companies. This methodology offers details of protein-ligand interactions at levels of resolution virtually unmatched by any other technique, and this approach holds the promise of novel, more effective, safer and cheaper drugs. Although crystallography remains a laborious and ra Read More

The aim of virtual high throughput screening is the identification of biologically relevant molecules amongst either tangible or virtual (large) collections of compounds. Amongst the various virtual screening approaches, those that are ligand based are becoming very popular due to the possibility to screen millions of molecules in a timely way. Descriptors and methods are briefly introduced and reviewed with more emph Read More

The Chemistry Development Kit (CDK) provides methods for common tasks in molecular informatics, including 2D and 3D rendering of chemical structures, I/O routines, SMILES parsing and generation, ring searches, isomorphism checking, structure diagram generation, etc. Implemented in Java, it is used both for server-side computational services, possibly equipped with a web interface, as well as for applications and client- Read More

A correct representation of intermolecular interaction energies is necessary for reliable drug-receptor docking studies. While ab initio quantum chemistry with extended basis sets is the most accurate tool for that purpose, its use is precluded for very large molecular complexes. This constitutes the incentive for the development of accurate molecular mechanics potentials, in which the first-order electrostatic, and the Read More

Family C of the superfamily of G-protein coupled receptors is a growing family of heptahelical receptors, which includes, among others, metabotropic glutamate receptors (mGluRs) and GABA(B) receptors. A common feature of all the members of family C is a structural architecture much more complex than any other GPCRs. Computational studies, including homology modeling, pharmacophore definitions and molec Read More

G protein-coupled receptors (GPCRs) represent the largest family known of signal-transducing molecules. They convey signals for light and many extracellular regulatory molecules. GPCRs have been found to be dysfunctional/ dysregulated in a growing number of human diseases and they have been estimated to be the targets of more than 40% of the drugs used in clinical medicine today. The crystal structure of rhodopsin Read More