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PubMed · 15597203

ProPose: a docking engine based on a fully configurable protein-ligand interaction model.

Markus H J Seifert·Frank Schmitt·Thomas Herz·Bernd Kramer
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Abstract

Virtual high-throughput screening of molecular databases and in particular high-throughput protein-ligand docking are both common methodologies that identify and enrich hits in the early stages of the drug design process. Current protein-ligand docking algorithms often implement a program-specific model for protein-ligand interaction geometries. However, in order to create a platform for arbitrary queries in molecular databases, a new program is desirable that allows more manual control of the modeling of molecular interactions. For that reason, ProPose, an advanced incremental construction docking engine, is presented here that implements a fast and fully configurable molecular interaction and scoring model. This program uses user-defined, discrete, pharmacophore-like representations of molecular interactions that are transformed on-the-fly into a continuous potential energy surface, allowing for the incorporation of target specific interaction mechanisms into docking protocols in a straightforward manner. A torsion angle library, based on semi-empirical quantum chemistry calculations, is used to provide minimum energy torsion angles for the incremental construction algorithm. Docking results of a diverse set of protein-ligand complexes from the Protein Data Bank demonstrate the feasibility of this new approach. As a result, the seamless integration of pharmacophore-like interaction types into the docking and scoring scheme implemented in ProPose opens new opportunities for efficient, receptor-specific screening protocols. [figure: see text]. ProPose--a fully configurable protein-ligand docking program--transforms pharmacophores into a smooth potential energy surface.

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Markus H J Seifert, Frank Schmitt, Thomas Herz, Bernd Kramer. 2004-10-08. ProPose: a docking engine based on a fully configurable protein-ligand interaction model.. https://doi.org/10.1007/s00894-004-0201-1

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