Prof. R. Sowdhamini

Computational Approaches to Protein Science

Genome sequencing projects have enormous potential for benefiting human endeavors. However, just as acquiring a language's vocabulary does not enable one to speak it, databases that list the amino acid composition of proteins do not directly tell us much about these proteins' higher-level structure and function. The most productive way to indirectly exploit these databases has been to start with the small number of proteins that are fully-characterised and to assume that other "similar" proteins will have a related structure and function. Proteins with very similar amino acid sequence are "no-brainers", but the real test, which our group largely focuses on, is to detect the "essential" similarity in proteins whose non-critical sections have experienced random rearrangements during evolution. In such cases functionally similar proteins may have less than 25% sequence overlap. To enable more complete tracing of protein family trees, we have developed and improved upon a wide range of computational methods: some can be applied to all proteins, others exploit characteristic features of specific protein types (e.g. the strong influence of disulphide bonds on the structure of extracellular proteins). These have been adapted into a number of widely used publicly-accessible web resources (e.g. DIAL, iMOT, MODIP, FMALIGN). Applying these and other techniques, we have also carried out within- and cross-genome surveys of the members of various entire protein families and superfamilies. Finally, we have been able to use our improved understanding of the functionally-significant regions of proteins for the theoretical prediction of protein function.

A peek at our work

Plant Genomics

Function Test Experiments

Ligand Screening

Caps Structure Team

Key Publications

[68] Bhadra, R., Sandhya, S., Abhinandan, K. R., Chakrabarti, S., Sowdhamini, R., & Srinivasan, N. (2006). Cascade PSI-BLAST web server: a remote homology search tool for relating protein domains. Nucleic acids research, 34(Web Server issue), W143–W146. https://doi.org/10.1093/nar/gkl157

[236] Iyer, M. S., Bhargava, K., Pavalam, M., & Sowdhamini, R. (2019). GenDiS database update with improved approach and features to recognize homologous sequences of protein domain superfamilies. Database : the journal of biological databases and curation, 2019, baz042. https://doi.org/10.1093/database/baz042

[250] Karpe, S. D., Tiwari, V., & Ramanathan, S. (2021). InsectOR-Webserver for sensitive identification of insect olfactory receptor genes from non-model genomes. PloS one, 16(1), e0245324. https://doi.org/10.1371/journal.pone.0245324 


[265] Bhattacharyya, T., Nayak, S., Goswami, S., Gadiyaram, V., Mathew, O. K., & Sowdhamini, R. (2022). PASS2.7: a database containing structure-based sequence alignments and associated features of protein domain superfamilies from SCOPe. Database : the journal of biological databases and curation, 2022, baac025. https://doi.org/10.1093/database/baac025

[126] Shameer, K., Shingate, P. N., Manjunath, S. C., Karthika, M., Pugalenthi, G., & Sowdhamini, R. (2011). 3DSwap: curated knowledgebase of proteins involved in 3D domain swapping. Database : the journal of biological databases and curation, 2011, bar042. https://doi.org/10.1093/database/bar042

[188] Sukhwal, A., & Sowdhamini, R. (2015). PPCheck: A Webserver for the Quantitative Analysis of Protein-Protein Interfaces and Prediction of Residue Hotspots. Bioinformatics and biology insights, 9, 141–151. https://doi.org/10.4137/BBI.S25928 


[95] Tripathi, L. P., & Sowdhamini, R. (2008). Genome-wide survey of prokaryotic serine proteases: analysis of distribution and domain architectures of five serine protease families in prokaryotes. BMC genomics, 9, 549. https://doi.org/10.1186/1471-2164-9-549

[250] Karpe, S. D., Tiwari, V., & Ramanathan, S. (2021). InsectOR-Webserver for sensitive identification of insect olfactory receptor genes from non-model genomes. PloS one, 16(1), e0245324. https://doi.org/10.1371/journal.pone.0245324

[211] Pasha, S. N., Meenakshi, I., & Sowdhamini, R. (2016). Revisiting Myosin Families Through Large-scale Sequence Searches Leads to the Discovery of New Myosins. Evolutionary bioinformatics online, 12, 201–211. https://doi.org/10.4137/EBO.S39880

[237] Sathyanarayanan, N., Cannone, G., Gakhar, L., Katagihallimath, N., Sowdhamini, R., Ramaswamy, S., & Vinothkumar, K. R. (2019). Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway. Nature communications, 10(1), 4127. https://doi.org/10.1038/s41467-019-11931-1

[219] Gangadharan, B., Sunitha, M. S., Mukherjee, S., Chowdhury, R. R., Haque, F., Sekar, N., Sowdhamini, R., Spudich, J. A., & Mercer, J. A. (2017). Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region. Proceedings of the National Academy of Sciences of the United States of America, 114(42), 11115–11120. https://doi.org/10.1073/pnas.1710354114

[91] Vyas, N., Goswami, D., Manonmani, A., Sharma, P., Ranganath, H. A., VijayRaghavan, K., Shashidhara, L. S., Sowdhamini, R., & Mayor, S. (2008). Nanoscale organization of hedgehog is essential for long-range signaling. Cell, 133(7), 1214–1227. https://doi.org/10.1016/j.cell.2008.05.026

[194] Upadhyay AK, Chacko AR, Gandhimathi A, Ghosh P, Harini K, Joseph AP, Joshi AG, Karpe SD, Kaushik S, Kuravadi N, Lingu CS, Mahita J, Malarini R, Malhotra S, Malini M, Mathew OK, Mutt E, Naika M, Nitish S, Pasha SN, Raghavender US, Rajamani A, Shilpa S, Shingate PN, Singh HR, Sukhwal A, Sunitha MS, Sumathi M, Ramaswamy S, Gowda M, & Sowdhamini R. (2015). Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties. BMC plant biology, 15, 212. https://doi.org/10.1186/s12870-015-0562-x

[232] Pasha, SN., Shafi, KM., Joshi, AG., Meenakshi, I., Harini, K., Mahita, J., Sajeevan, RS., Karpe, SD., Ghosh, P., Nitish, S., Gandhimathi, A., Mathew, OK., Prasanna, SH., Malini, M., Mutt, E., Naika, M., Ravooru, N., Rao, RM., Shingate, PN., Sukhwal, A., Sunitha, MS., Upadhyay, AK., Vinekar, RS., & Sowdhamini, R. (2020). The transcriptome enables the identification of candidate genes behind medicinal value of Drumstick tree (Moringa oleifera). Genomics, 112(1), 621–628. https://doi.org/10.1016/j.ygeno.2019.04.014

[245] Kalmankar, N. V., Venkatesan, R., Balaram, P., & Sowdhamini, R. (2020). Transcriptomic profiling of the medicinal plant Clitoria ternatea: identification of potential genes in cyclotide biosynthesis. Scientific reports, 10(1), 12658. https://doi.org/10.1038/s41598-020-69452-7 

Address

Lab 25 NCBS
Tata Institute of Fundamental Research
Bellary Road
Rajiv Gandhi Nagar, Kodigehalli
Bengaluru, Karnataka 560065


Contacts

Email: mini[at]ncbs[dot]res[dot]in
Phone: 080 2366 6251