Influence of Disease-Causing Mutations on Protein Structural Networks

Prabantu, VM and Naveenkumar, N and Srinivasan, N (2021) Influence of Disease-Causing Mutations on Protein Structural Networks. In: Frontiers in Molecular Biosciences, 7 .

Preview	PDF fro_mol_bio_7_2021.pdf - Published Version Download (1MB) | Preview
	Microsoft Word datasheet1_Influence of Disease-Causing Mutations on Protein Structural Networks.docx - Published Supplemental Material Download (1MB)

Abstract

The interactions between residues in a protein tertiary structure can be studied effectively using the approach of protein structure network (PSN). A PSN is a node-edge representation of the structure with nodes representing residues and interactions between residues represented by edges. In this study, we have employed weighted PSNs to understand the influence of disease-causing mutations on proteins of known 3D structures. We have used manually curated information on disease mutations from UniProtKB/Swiss-Prot and their corresponding protein structures of wildtype and disease variant from the protein data bank. The PSNs of the wildtype and disease-causing mutant are compared to analyse variation of global and local dissimilarity in the overall network and at specific sites. We study how a mutation at a given site can affect the structural network at a distant site which may be involved in the function of the protein. We have discussed specific examples of the disease cases where the protein structure undergoes limited structural divergence in their backbone but have large dissimilarity in their all atom networks and vice versa, wherein large conformational alterations are observed while retaining overall network. We analyse the effect of variation of network parameters that characterize alteration of function or stability. © Copyright © 2021 Prabantu, Naveenkumar and Srinivasan.

Item Type:	Journal Article
Publication:	Frontiers in Molecular Biosciences
Publisher:	Frontiers Media S.A.
Additional Information:	The copyright for this article belongs to Authors
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	20 Apr 2021 09:11
Last Modified:	20 Apr 2021 09:11
URI:	http://eprints.iisc.ac.in/id/eprint/68637

Actions (login required)

View Item