An alteration in the amino acid sequence can bring about changes in the folding and stability of the protein ( Lorch et al., 1999 Lorch et al., 2000), interaction of the protein with other molecules ( Rignall et al., 2002 Ung et al., 2006) and change in functional levels ( Tiede et al., 2006) or overall function of the protein as well. The amino acid sequence determines the protein 3-D structure ( Anfinsen, 1973) which is related to its function. We analyse the effect of variation of network parameters that characterize alteration of function or stability. 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 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. 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 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. In this study, we have employed weighted PSNs to understand the influence of disease-causing mutations on proteins of known 3D structures. A PSN is a node-edge representation of the structure with nodes representing residues and interactions between residues represented by edges. The interactions between residues in a protein tertiary structure can be studied effectively using the approach of protein structure network (PSN). 3Bharathidasan University, Tiruchirappalli, India.2National Centre for Biological Sciences, TIFR, Bangalore, India.1Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Vasam Manjveekar Prabantu 1, Nagarajan Naveenkumar 1,2,3 and Narayanaswamy Srinivasan 1*
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