Title: Designing of suitable linkers for the chimeric proteins to achieve the desired flexibility and extended conformation

Authors: Manoj Patidar; Naveen Yadav; Sarat K. Dalai

Addresses: Institute of Science, Nirma University, Ahmedabad 382481, India ' Institute of Science, Nirma University, Ahmedabad 382481, India ' Institute of Science, Nirma University, Ahmedabad 382481, India

Abstract: The designing and production of therapeutic chimeric proteins is the central focus area of many industrial R & D and research institutes. The efficient productions of chimeric proteins not only require suitable domains or partner proteins and intact receptor binding sites, but the selection of linkers is equally important. The linkers are essential to provide space between two domains, prevent from steric hindrance and most importantly to make the chimeric proteins flexible. In this in silico study, we have systematically designed various linkers, tested their feasibility and evaluated their essentiality. Here, we fused cytokine of interest (i.e., IL-2) with IgG1 Fc via various linkers. We designed linkers of various lengths and amino acid composition and tested their ability to provide the extended conformation and desired flexibility and also to minimise the conformational changes. Additionally, we have evaluated the role of the linker in dimerisation of chimeric proteins. We next tested the influence of linkers on stability and functionality of chimeric proteins.

Keywords: chimeric proteins; linker; immunoglobulin; protein engineering; dimerisation.

DOI: 10.1504/IJCBDD.2018.094632

International Journal of Computational Biology and Drug Design, 2018 Vol.11 No.3, pp.236 - 254

Received: 01 Aug 2017
Accepted: 21 Nov 2017
Published online: 10 Sep 2018 *

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