Off-Pump Coronary Artery Bypass Surgery Induces Prolonged Alterations to Host Neutrophil Physiology

Abstract

A pharmacophore represents a simple and intuitive concept that have been used for decades in medicinal chemistry. The use of three-dimensional chemical feature ensembles provides transparency through the ease of interpretability and at the same time allows for efficient implementation of high-throughput virtual screening methods. 3D pharmacophores have routinely been used in combination with other molecular modelling techniques, such as quantiative structure-activity relationships or pseudo-receptor modeling. The synergistic application of different approaches in drug discovery workflows may allow to fully exploit their advantages, while compensating for some of the intrinsic limitations of each methodology. Whereas, in the past, pharmacophore models have been mainly generated using ligand-based strategies, novel programs have been developed and applied successfully in the last few years, by combining structure-based and pharmacophore-based approaches. This is mainly influenced by the rapidly growing number of protein-ligand 3D structures that are the basis for such combined approaches. This chapter will include a general introducion in pharmacophore and pseudo-receptor modelling, several success stories and an outlook to future developments.