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 binding mode. In this study we would like to introduce an implementation of interaction profiles⁽¹⁾based on Structural Interaction Fingerprints (SIFt)⁽²⁾to analyze known ligands docking poses within mGluR2 model. The use of interaction patterns allows precise and rapid binding site description.

The mGluR family consists of eight proteins divided into three groups corresponding to sequence similarities, pharmacology and physiological role. These groups are: I (mGluR1, -5), II (mGluR2, -3) and III (mGluR4, -6, -7, -8). Group II lies in field of our interest due to its potential as therapeutic target for antidepressant and anxiolytic drugs. Research was performed on population of 100 mGluR2 models created on Rhodopsin crystal structure template. Building that many virtual receptors provided us with semi conformational search on residues assembling incriminated receptor. Library of 179 known allosteric modulators of group II mGluR was used for docking studies and thus forging the binding mode.

Acknowledgments

The study was partly supported by a grant PNRF-103-AI-1/07 from Norway through the Norwegian Financial Mechanism, and by the Polish Ministry of Science and Higher Education (MNiSW), Grant No. N N405 184635.

1. Chuaqui C, Deng Z, Singh J „Interaction Profiles of Protein Kinase-Inhibitor Complexes and Their Application to Virtual Screening”, J. Med. Chem. 2005, 48, 121-133
2. Deng Z, Chuaqui C, Singh J „Structural Interaction Fingerprint (SIFt): A Novel Method for Analyzing Three-Dimensional Protein-Ligand Binding Interactions”, J. Med. Chem. 2004, 47, 337 -344

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