3D Structure Generation, Molecular Dynamics and Docking Studies of IRHOM2 Protein Involved in Cancer & Rheumatoid Arthritis

Author(s): Utkarsh Raj, Himansu Kumar, Pritish Kumar Varadwaj

Journal Name: Current Computer-Aided Drug Design

Volume 11 , Issue 4 , 2015

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A short-lived membrane protein IRHOM2 pedals a cascade of events by regulating Epidermal Growth Factor Receptor (EGFR) signalling in parallel with metalloproteases which results their involvement in cancer as well as in rheumatoid arthritis. Therefore, IRHOM2 is a potential therapeutic drug target for these diseases, but its 3D-structure has not been reported yet. In this study, the three-dimensional structure of the IRHOM2 protein was generated using I-TASSER (Iterative Threading Assembly Refinement) server. The modeled structure of IRHOM2 receptor was validated using various Structural Analysis and Verification Server (SAVES) in which 99.7% of amino acid residues are present in the favoured regions of the Ramachandran Plot. Further, the refined modeled structure was subjected to molecular dynamics simulation & docking analysis. Virtual screening studies were carried out using Glide with various selective libraries containing 24552 compounds and the analysis indicated extensive hydrogen bonding network and hydrophobic interactions which play a significant role in its binding. Docking results were analyzed for high ranking compounds using a consensus based docking score to calculate the binding affinity as a measure of protein–ligand interactions. The top ranking molecule against IRHOM2 active site has a glide g-score of -12.565 kcal/mol and glide e-model score of -74.967 with 3 hydrogen bonds and 11 hydrophobic contacts. This compound may act as probable inhibitor against these chronic diseases but further in vitro studies are required.

Keywords: Docking, EGFR, IRHOM2, ITASSER, SAVES, simulation, virtual screening.

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Article Details

Year: 2015
Page: [325 - 335]
Pages: 11
DOI: 10.2174/1573409912666151124234008
Price: $65

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