Alladi Ramakrishnan Hall

Bioinformatics approaches for understanding mutational effects on protein structure and function: implications to diseases

M. Michael Gromiha

Department of Biotechnology, IIT Madras

The substitution of amino acid residues in a protein alters its structure, stability and function, and may lead to diseases (1,2). We have developed comprehensive databases for understanding protein structure and function (3,4), and annotating disease-causing mutations in globular and membrane proteins using experimental data reported in the literature (5,6). These databases provide a description of mutants, structural and functional features along with visualization, search, display, and download options. We have systematically analyzed the effect of these mutations at protein level on change in stability, binding affinity and disease-causing. Utilizing the information, we have developed computational methods for predicting the change in binding affinity and identifying disease causing mutations in proteins (7,8). These methods have been utilized for identifying the potential driver and passenger mutations at a large scale, which could be used for designing experiments. The salient features of the results will be discussed.

References:
(1) M.M. Gromiha (2010) Protein Bioinformatics: from sequence to function, Elsevier/Academic Press.
(2) M.M. Gromiha (2020) “Protein Interactions”, World Scientific, Singapore
(3) K. Harini, A. … M. Michael Gromiha (2022) Nucl. Acids Res. 50:D1528-D1534.
(4) R. Nikam, … M. Michael Gromiha (2021) Nucl. Acids Res. 49, D420-424.
(5) A. Kulandaisamy, … M.M. Gromiha (2018) Bioinformatics 34, 2325-2326
(6) K. Ganesan, … M. M. Gromiha (2019) PLoS ONE 14(1), e0210475.
(7) S. Jemimah, M. Sekijima and M. Michael Gromiha (2020) Bioinformatics 36:1725-1730
(8) N.R.S. Shanmugam, K. Veluraja and M. Michael Gromiha (2022) J. Mol. Biol. 434, 167526
(9) A. Kulandaisamy, … M. Michael Gromiha (2020) Human Mutation 41, 581-590.
(10) M. Pandey … M.M. Gromiha (2022) Brief. Bioinf, 23, bbac451