Volume 3 Supplement 1

6th German Conference on Chemoinformatics, GCC 2010

Open Access

Rapid binding site analysis by means of structural interaction fingerprint patterns – an implication to GPCR-targeted CADD

Journal of Cheminformatics20113(Suppl 1):P42

DOI: 10.1186/1758-2946-3-S1-P42

Published: 19 April 2011

One of the most troublesome stages of Computer Aided Drug Design (CADD) process is analyzing huge amount of data provided by docking studies. Simple scoring functions alone can provide only shallow information about ligand-receptor interactions, since they do not distinguish neither residues nor single atoms. Very often a visual inspection is the only way to determine a binding mode. Here, we introduce an implementation of interaction profiles [1] based on Structural Interaction Fingerprints (SIFt) [2], which allow precise and rapid binding site description.

SIFts employed in our modelling agenda form a nine-digit binary pattern for each amino-acid in the receptor, covering all major types of interactions.

Computed over an ensemble of ligands and/or receptor conformations, averaged real number SIFt elegantly depicts overall preferences towards particular interactions. This enables construction of a compact scheme of crucial forces involved in ligand-receptor complex formation, which then facilitate design of a binding mode hypothesis and description of preferred ligand positions within the active site. An application is presented basing on a model of an allosteric domain of mGluR4 receptor [3] – a challenging computational task, due to untrivial evolutionary relationships for homology model construction purposes, and shortage of experimental data for hypotheses validation.

Declarations

Acknowledgements

This study is supported by project UDA-POIG.01.03.010-12-100/08-00 co-financed by European Union from the European Fund of Regional Development (EFRD).

Authors’ Affiliations

(1)
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences

References

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Copyright

© Kosciolek et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.