Title: Insights into CFTR structural properties and dynamic nature of regulatory domain using computational approach

Authors: Vasavi Garisetti; Arthikasree Anandamurthy; Roslin Elsa Varughese; Gayathri Dasararaju

Addresses: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India ' Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India ' Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India ' Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India

Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a multi-domain ion channel which is a part of the ATP-binding cassette (ABC) superfamily. The ion channel is regulated by phosphorylation of its regulatory domain (R) and binding of adenosine triphosphate (ATP) to the nucleotide binding domains. We have predicted the model of the complete CFTR including the R domain using AlphaFold2 and have studied the behaviour of different domains of the predicted model in a simulated dynamic environment with POPC lipid bilayers for 200 ns. A combination of free energy landscapes, principal component and comparative structural analyses were used to gain a broad perspective of the protein's conformational properties. The CFTR R domain, which is disordered, lacks a suitable 3D structure; this is the basis for the current study. The process of utilising new tools will provide a fresh viewpoint on how to comprehend the dynamic nature of the R domain and also provide insights into the structural characteristics of CFTR.

Keywords: cystic fibrosis; cystic fibrosis transmembrane conductance regulator; CFTR; R domain; intrinsically disordered proteins; molecular dynamics simulation; transmembrane protein.

DOI: 10.1504/IJBRA.2023.132629

International Journal of Bioinformatics Research and Applications, 2023 Vol.19 No.2, pp.83 - 104

Received: 05 Dec 2022
Accepted: 08 Feb 2023
Published online: 31 Jul 2023 *

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