New Features that Improve the Pharmacophore Tools from Accelrys

Jon      Sutter; Jiabo      Li; Allister      J. Maynard; Anne      Goupil; Tien      Luu; Katalin      Nadassy

Abstract

Generating a pharmacophore is often the first step towards understanding the interactions between a receptor and a ligand and can be pivotal to a successful drug discovery project. The pharmacophore tools at Accelrys have been used to assist in many different projects over the years, such as lead generation, scaffold hopping, mining ligand databases as well as many more. In this article, we will review the pharmacophore tools that have been developed at Accelrys. These will include the often used and well validated ligand based algorithms, HipHop and HypoGen and as well as extensions of these algorithms, HipHopRefine and HypoGenRefine. Recently we also developed new pharmacophore tools in the area of structure based design – deriving pharmacophores from the receptor as well as the receptor-ligand complex – which will also be discussed in this paper.

Keywords: Fragment-based design, receptor-ligand pharmacophore, structure-based pharmacophore, scaffold hopping, mining ligand databases, algorithms, pharmacophore tools, structure based design, receptor-ligand complex, 2D SAR