Current Pharmaceutical Design - Volume 8, Issue 17, 2002

The recent success of the first FDA-approved small-molecule tyrosine kinase inhibitor Gleevec (STI-571, imatinib mesylate) in the treatment of chronic myelogenous leukemia (CML) has focused attention on the potential therapeutic usefulness of inhibitors of other kinase targets. This review shall highlight recent applications of computational chemistry methods, comprising both ligand-based and structure-based approaches, i Read More

Since ancient times the operation of the brain has elicited more than usual interest. Data mining of the human genome is revealing that many CNS abnormalities have a genetic component. As yet this information can not be used directly to cure or ameliorate specific CNS disorders although this is regarded as having great potential for future therapies.Current CNS drug design and 3D QSAR is based on knowing either the structur Read More

Receptor-based drug discovery can increase the novelty of a hit list over ligandbased models that are dependent on known inhibitors. It is important to explore new conformational and chemical space, but it is difficult to predict the plasticity of the binding site. Receptor-based methods are usually based on crystal structures of ligand-protein complexes, and hit lists can be restricted to the size and shape of the receptor model. Man Read More

The review deals with the problem of the study of ligand-receptor interactions and the use of Molecular Dynamics (MD) simulation to approach such a problem. After a short review of the fundamentals of MD we describe the medium in which all biology takes place, water. Emphasis is put on the water models appropriate for simulation of macromolecular systems explicitly including the water molecules. We consider the quality of Read More

The basic principles of 3-D quantitative structure-activity relationships (QSARs) analysis are discussed in the light of the fuzzy logic concept. According to that concept, the traditionally “one chemical - one structure - one parameter value” relationship in QSAR is suggested to be modified into “one chemical - finite set of structures - range of parameter values” principle. In this respect, two recently developed techniques ac Read More