Protein folding is one of the most complicated tasks around. And although Google DeepMind has solved the 50-year-old grand challenge of protein folding with AlphaFold, it is far from completely resolved. However, another important name that comes to the mind is Wolfram. The Wolfram Language had multiple functions to visualise proteins and their related components. The MoleculePlot and MoleculePlot3D functions can be used for 2D and 3D visualisation of amino acids.

Additionally, ResourceFunctions like BioSequenceMoleculePlot and BioSequenceMoleculePlot3D can be used for polypeptide visualisation and BioMoleculePlot3D for ribbon diagrams of proteins. In the coming months, other functions will be added to the language to make it more comprehensive for protein structure analysis.

Recently, Soutick Saha, a bioinformatics developer at Wolfram, created the Wolfram ProteinVisualisation paclet—a powerful tool that brings the intricate world of bio-molecular structures. The most amazing thing about this resource is he could do it in just five months, thanks to the accessibility and power of the Wolfram Language.

The Wolfram ProteinVisualisation paclet is a comprehensive collection of functions for an immersive exploration and visualisation of complex 3D bio-molecular structures. It allows users to delve into molecular backbones, compute vital features like contact maps and dihedral angles, and analyse proteins, nucleic acids, and their complexes. With eleven functions, this tool enables visualisation of protein backbone atoms, amide planes, dihedral angles, protein contact maps, and more. It is an important discovery that will aid more research in structural biology.  

Analytics India Magazine caught up with Saha to understand more about his breakthrough, his academic journey and more.

A Small-town Boy Shaping the Future of Protein Research

Currently based in Champaign, Illinois, Saha was born and raised in Kalna, a small town in West Bengal. He completed his schooling at the esteemed Ramakrishna Mission Vidyalaya, Narendrapur, an experience he considers “highly rewarding” as the boarding school environment fostered independence in both thought and decision-making from an early age.

“Existing software and packages have one or two of these functions, and researchers often have to use multiple of them at the same time for protein structure analysis and visualization. To address this, I created the Wolfram ProteinVisualisation paclet, aiming to consolidate these functions in one place. It is a work in progress and will become more comprehensive over time,” said the IIT-Madras alumnus. 

However, he would not call the paclet a discovery, but a very useful resource that will make the fascinating world of protein structures accessible to a wide range of people, from beginners to experts.

He added that the first function he developed was the ProteinContactMap and soon enough one function progressed into a paclet with eleven functions in five months. The Wolfram Language is very versatile but at the same time easy to master. It has functions for 2D and 3D visualisations, geometry, and chemistry and all these preexisting functions allowed him to develop this paclet in a very short time.

“Having worked with six different languages over the past 12 years, Wolfram is the easiest to work with for seamlessly combining data, chemistry, math, geometry, and interactive visualisation,” he added. 

Transitioning from Physics to Biology

During his high school years, Saha stumbled upon the iconic “Fundamentals of Physics” by Halliday, Resnick, and Walker, making him eager to work on the connection between physics and nature. “As I delved into organic and physical chemistry, I realised that physics offered the broadest scope, encompassing everything from subatomic particles to the vastness of the universe. Its relevance across space and time made it even more compelling, solidifying my decision to pursue physics as my primary field of study,” he added.

He went on to complete graduation from Chennai Mathematical Institute (CMI). Following his time at CMI, he took a master’s degree in physics at the Indian Institute of Technology (IIT) Madras. “It was there that my girlfriend (now wife) inspired me to venture into biophysics,” he laughed. And that is how he switched from physics to biology. “I switched from studying physics to researching theoretical biophysics and computational biology. Combining my physics background with computer and math skills, I found the challenges and fascinations of biological problems intriguing,” said the 30-year-old. 

Subsequently, he pursued a PhD in physics at Purdue University, knowing that his true passion lay in theoretical biophysics and computational biology. 

But the person instrumental in helping Saha at every step was his advisor Dr Andrew Mugler, who mentored him on how to break down problems and approach them from a physics standpoint. “This involved converting problems into mathematical equations and applying principles of physics to solve them. This was the most significant lesson I learned during my PhD and I continue to carry it with me wherever I go,” he added. 

How Wolfram Happened

Soon, he discovered that his strength lay in solving quantitative problems beyond biophysics and landed up at Wolfram for an internship. He was tasked to reproduce and develop protein ribbon diagrams using the Wolfram language. He broke down the problem, understood the data structure, delved into biophysics and geometry, and used geometric problem-solving and vector algebra. 

During his PhD, his work revolved around the different aspects of understanding cancer cell movement and metastasis, and cell signaling in bacteria. He also explored the roles of different molecules and motifs and did theoretical research on simple molecules and mechanisms to explain complex cellular behaviors, building on previous experimental collaborations. 

Upon rejoining Wolfram in January this year as a full-time employee, he began working on refining and expanding the ideas he had initiated during the internship. “Despite my limited experience, Wolfram saw the potential in me and gave me the opportunity to excel,” he said. 

Saha believes that working at Wolfram has had a tremendous positive impact on his intellectual and career growth, especially because of the collaborative and supportive team culture. “Publishing my project at Wolfram allows me to embrace open-source culture, get credit for my work, and freely promote it. This privilege is rare in today’s companies, and I’m grateful for the opportunities it brings,” Saha commented. 

Reflecting on his journey and acknowledging his humble background, Saha believes that his success stems from a combination of hard work, good opportunities, and the support of those around him. “I have always been driven by hard work. These three elements—hard work, good opportunities, and supportive people—have propelled me to where I stand today,” he concluded.

Read more: Decoding the Stephen Wolfram Enigma