Usefulness and Robustness of In Silico and Experimental Technology for Drug Discovery

Contrary to the previous issues on "Pharmacophore Elucidation & their use in Drugs & Design: Experimental Structures, Conformational Analysis and 3D QSAR", mostly with a computational character we decided to move a bit and invite scientists who use approaches where the conformational problem was not the end point but lies in the black box of a more wider context finally leading to the “drug”. Ideally the issue can be viewed as a kind of drug design cycle where some approaches are employed that do not exclude but can mutually complement each other. The article by Edward Zartler et al. on “Protein NMR as a screening tool in drug discovery” integrates well with both by A. Goldblum et al. on “Computational protein design” and by Walter Huber et al., which reviews on the state of art of the Surface Plasmon Resonance (SPR) technology. Advances in protein manipulation, whether by biological means (labelling) or physical means (NMR), has become prominent within the past ten years and has created a powerful method which is able to observe ligand-target interactions in solution. Protein based NMR methods have the advantage of supplying detailed structural information in addition to readout of binding events. Computational protein design has emerged in recent years as a field that could make a substantial impact on the design of protein drugs. Surface Plasmon Resonance (SPR) technology has widespread applications in many fields of the drug discovery process. Protein/protein interactions can be monitored in real time when working with biopharmaceuticals as well as protein/small analyte interactions during hit finding, secondary screening, lead optimization and lead selection. Equilibrium binding constants, kinetic rate constants and thermodynamic parameters are obtained from such studies that help to understand the mechanism of the binding reactions. This information can be directly used to improve binding. The final “last but not least” article by Gloria Uccello Baretta et al. points out the role of chirality with respect to the therapeutical and regulatory effects of pharmaceutical products that has led to a growing demand for reliable direct methods for monitoring stereoisomeric products. The analysis of enantiorecognition processes involves the detection of enantiomeric species as well as the study of chiral discrimination mechanisms. In both fields Nuclear Magnetic Resonance (NMR) spectroscopy plays a fundamental role, providing several tools, based on the use of suitable chiral auxiliaries, for observing distinct signals of enantiomers and for investigating the complexation phenomena involved in enantiodiscrimination processes.