The binding properties of the human PKAI protein as inferred from molecular modeling and Molecular dynamics study In Silico analysis of human PKAI protein

DOI: 10.5176/978-08-8227-3_BICB2011-31

Authors: Karthikeyan Muthusamy, Palani Kirubakaran and Selvaraman Nagamani

Abstract:

PKAI or cAMP-dependent protein kinase type I-alpha (PRKAR1A) is a regulatory subunit, which is encoded by the gene PRKAR1A. PRKAR1A gene is over-expressed in different types of tumor and cancer cells. The PKAI protein is identified as a one of the potential candidate for anti cancer drug target. Human PKAI protein was modeled using comparative homology modeling using protein kinase A (Pdb id: 2QCS) as a reference template. The refinement of the model was carried out through molecular dynamics simulations by Desmond software. The reliability of the model was further assessed by PROCHECK and ProSa II analysis, which are in acceptable range. The PKAI binding groove was checked by small ligand molecules leading to inhibition. Virtual screening analysis was performed by various available small molecule databases (NCI and Asinex) and we have found that five of the compounds show promising docking score (glide sore and energy) which are in acceptable range of ADME properties. Further characterisation will be carried out by in vitro and in vivo assays.

Keywords: PRKAR1A, Molecular dynamics, Molecular docking