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Research Journal of Pharmacy and Technology
Year : 2017, Volume : 10, Issue : 9
First page : ( 3089) Last page : ( 3094)
Print ISSN : 0974-3618. Online ISSN : 0974-360X.
Article DOI : 10.5958/0974-360X.2017.00548.0

Deciphering the impact of R324L Mutation in Polycystin-1PKD Domain associated with Autosomal Dominant Polycystic Kidney Disease(ADPKD): A Molecular Dynamics Perspective

Anbarasu K.1, Senthilkumar D.2, Jayanthi S.3,*

1Department of Bioinformatics, School of Life Sciences, VELS University, Chennai. 600 117, Tamil Nadu, India

2Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore. 632 014, Tamil Nadu, India

3Department of Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India

*Corresponding Author E-mail: jayss66@gmail.com

Online published on 16 May, 2018.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the gradual development of multiple cysts through both kidneys. The normal kidney tubules cavities filled with fluid portions and lead to progressive renal impairment, frequently with the additional problems of hypertension, infection, and pain which leads to kidney failure. The mutation of PKD1 gene and its product polycystin-1, a membrane-bound multi domain protein mainly cause ADPKD. Hence, our study attempted to investigate the impact of structural and atom level changes in polycystin-1 PKD domain due to critical mutation R324L in the dynamic system. Using the powerful computational techniques like mutation modeling, molecular dynamics (MD) simulations and principal component analysis (PCA) are followed for the comparison of wild type protein and mutant R324L. The trajectory analysis from 50 ns simulation results showed the major conformational changes in atomic level of mutant protein that significantly affects the function of polycystin-1. Moreover, principal component analysis elucidated the abrupt change in overall motion of the protein due to mutation. Thus, our study deciphered the mutation R324L drastically affects the polycystin-1 in structural level and plays critical in ADPKD mechanism.

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Keywords

Autosomal dominant polycystic kidney disease, Polycystin-1, Mutation, Molecular dynamics simulation, Principal component analysis.

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