Current Computer - Aided Drug Design - Volume 4, Issue 2, 2008

Modern drug discovery has contributed much to the progress of medicine and well being of societies during the past century. Generally, a disease relevant macromolecule is studied first in vitro, in cells and in whole organisms, and evaluated as a potential drug target for a specific therapeutic intervention. Medicinal chemistry projects then commence by the search and identification of a binding partner for the single macromol Read More

Since the advent of QSAR (quantitative structure activity relationship) modeling quantitative representations of molecular structures are encoded in terms of information-preserving descriptor values. Nowadays, a nearly infinite variety of potential descriptors is available and descriptor selection is no longer a task which can be done manually. There is an increasing need for automation in order to reduce the dimensionality of the d Read More

The various contributions to binding energies for cytochrome P450 enzyme-substrate interactions are discussed in the light of intermolecular forces of attraction in biological systems. These energies include: electrostatic, van der Waals, hydrogen bond, π-π stacking and desolvation processes. These individual components can be used to estimate the binding energies of P450 substrates, and the example of camphor in CYP101 i Read More

The olfactory system has sophisticated molecular mechanisms for recognizing and discriminating an enormous number of odorants. The detection of odorants in mammals is mediated by several hundreds of olfactory receptors (ORs), which comprise the largest superfamily of G-protein-coupled receptors (GPCRs) in the genome. Because GPCRs are major targets for therapeutic application, ample experimental data and compute Read More

QSAR modeling, a powerful method for the computer - aided drug design, demands appropriate choice of molecular structure description. At present thousands descriptors of molecular structure are suggested in QSAR and QSPR approaches. The selection of a subset of the most relevant molecular descriptors, used as variables, is important step in model development. In this short review recently reported algorithms for v Read More

Target-based drug design uses available 3D structural information of receptor molecules to either dock putative ligand molecules to receptor binding sites or to de-novo design new ligands. In many cases accurate prediction of putative binding geometries requires the appropriate inclusion of conformational flexibility of both the ligand as well as the receptor structure. The problem of appropriate treatment of conformationa Read More