Biophysical Society Bulletin | March 2024

Biophysicist in Profile

Ragothaman M. Yennamalli Areas of Research Structural bioinformatics, systems biology, and machine learning

Institution SASTRA Deemed University, India

At-a-Glance

Ragothaman M. Yennamalli is a computational biologist with more than a decade of experience in predictive modelling and biomolecular simulation projects. After the completion of his PhD degree from the prestigious Jawaharlal Nehru University, he gained more experience as a postdoctoral research associate at Iowa State University, University of Wisconsin–Madison, and Rice University, before settling into his current position as an assistant professor at SASTRA Deemed University.

Ragothaman M. Yennamalli

Ragothaman M. Yennamalli grew up in Madras, now called Chennai, in India. His father was an army accounts officer, so the family moved around often in Yennamalli’s youth. “My childhood experiences involved lots of traveling and settling in new places. An advantage of this exposure was that geog raphy for me was never a limitation. I could adapt to new environments easily. Also, I made new friends everywhere we went,” he says. “During our years in the Andaman and Nicobar Islands, I was exposed to the diverse and wild fauna and flora these islands had. The green geckos and a unique antiseptic plant are unique to these islands. Trying to identify the wild ones, looking at coral reefs, and cohabiting with snakes and centipedes made me curious about biology, in general.” His family is made up of artists and educators. Before his army position, his father had been a teacher for years; his mother worked as a primary school teacher. “Three genera tions of painters left an indelible mark on me, right from my grandfather, my mom, to my brother, who are full-fledged artists. Our dinner table conversations would be mostly about art, music, dance, and K. L. Saigal songs,” he recalls. “My par ents did not pressure me into becoming something specific. They gave full freedom to my brother and me in choosing our own paths. That privilege of choice was hugely important for me.” After high school, he studied microbiology at the University of Madras, then went on to earn a master’s degree in micro biology from Madurai Kamaraj University (MKU). Following his master’s studies, he studied bioinformatics at Jawaharlal Nehru University (JNU), eventually earning his PhD. “The science discussions in MKU and JNU over coffee and tea at the canteen opened my mind unlike elsewhere,” Yennamalli says. “During my master's, we had a course on structural biology and those pretty pictures of proteins fascinated me a lot! In my PhD I had decided that I would work on something related to protein structures. I learned during my coursework that computational structural biology had topics on crystal lization and space groups. It was very fascinating to me and

opened a new world to me. At that time, a new collaboration was started between JNU and the University of Queensland in Brisbane, Australia. I was nominated and I ended up studying protein structures at Bostjan Kobe and Paul Young ’s lab, spe cifically about the envelope protein of dengue virus. Dengue viral fever is endemic to both India and Australia. I took that as a PhD project and worked towards finding a drug that could help millions back home. I studied how the E protein undergoes conformational change using molecular dynamics simulations. Also, using a structure-based drug design ap proach we identified a promising lead compound that worked in experimental setup. The guidance I received from Naidu Subbarao as a supervisor was invaluable.” He next undertook a postdoctoral position with Alok Bhat tacharya at JNU working on drug-resistant Mycobacterium tuberculosis genomes. Then he moved to Iowa State Universi ty (ISU) to work with Taner Z. Sen on a carbohydrate-degrading enzyme called endoglucanase. “While my work was compu tational in nature, I collaborated with experimentalists, and I was involved in multiple projects. This helped me acquire many different technical skills in the domains of systems bi ology and machine learning,” Yennamalli explains. “To enhance my experience and to work in a large team, I worked with George N. Phillips, Jr. at the University of Wisconsin–Madison. I was involved with a multi-institutional structural genomics project on natural product biosynthetic pathway proteins… Later, George moved to Rice University, and I moved as well to set up the computational part of his lab and continued the same project.” Yennamalli is now an assistant professor at SASTRA Deemed University, a primarily undergraduate institution in the south of India. His position is equal parts teaching and research. Currently, he is studying the structure and function of redox enzymes called lytic polysaccharide monooxygenases (LP MOs) that have an unusual flat surface as part of their active site. “I am using machine learning algorithms to classify these LPMOs into various families,” he reveals. “I also work

March 2024

4

THE NEWSLETTER OF THE BIOPHYSICAL SOCIETY