Expediting drug development using molecular structure

Crystallography, the study of atomic and molecular structure, has gained widespread recognition lately. Derived from the Greek words crystallon, meaning cold or frozen drop, and graphein, meaning the experimental science of finding out the arrangement of atoms in solids, it is a technique used to determine the structures of large bio-molecules such as proteins. The valuable contributions of these methods to our understanding of many areas of science even led to 2014 being declared as the International Year of Crystallography by the United Nations.

The Indian Institute of Science (IISc), Bengaluru is witness to the work of generations of biological crystallographers using bio-molecules to address a variety of issues. The trend is well upheld by B Gopal and his research scholars at the Molecular Biophysics Unit (MBU), along with many other scientists. After dabbling in physics, biophysics, and immunology, Gopal ventured into the industry with his own start-up. But, for the last 14 years, he has supervised research at the MBU, successfully integrating areas of molecular microbiology, structural biology, protein chemistry and proteome analysis, with chemists, physicists and biologists, all under one roof.

Techniques like crystallography allow researchers to make continuous changes in the structure of proteins or other bio-molecules until they start to crystallise. These methods help demonstrate how ligands or drugs affect proteins. However, the main limiting step is to get the proteins to crystallise. “It is a bit like gambling,” he says.

This knowledge is applied to understand processes like transcriptional regulation, cellular communication, and antimicrobial resistance, among others. He laments that for all the dramatic strides in research and technology, in a country of more than 1.4 billion people, and numerous upcoming and well-established labs and companies, we cannot yet lay claim to any genuinely game-changing drug developed in India.

The major menaces like tuberculosis and effects of multi-drug resistant Staphylococcus aureus continue to pose a serious threat to health care. The humongous amounts of drugs and steroids that are outsourced are turning developing countries into toxic dumps without providing any real solution. Although enzyme engineering could potentially do away with a lot of these issues, the cost factor still remains.

Gopal believes that “the choice of any problem can have many variables put together, so if you cannot do everything, look for a niche to work in.” The lab collaborates with both clinicians and companies to conduct research on how drugs can be designed and effectuated effectively. To further their efforts in this area, Gopal and his colleagues have co-founded a company called Biosynth. This endeavor aims to utilise enzymatic processes for the synthesis of active pharmaceutical ingredients. Their ultimate objective is to make people accept cleaner strategies to develop drugs by making them more attractive.

Gopal strongly agrees that after a point, demarcations between physics and biology, or between applied and basic sciences become irrelevant. He stresses that the work his research team does would be an asset to both science and the industries, and also hopes that at least some of them would go out into the world to become
entrepreneurs and have the courage to take a leap of faith. “The techniques after all are not something super-complicated, it is the underlying thought that counts,” he believes. After all, science is a unified field, and that present and future scientists must be open to an interdisciplinary approach to address scientific problems.

He also adds that conducting research and discovering new ways to fight diseases is just half of the battle. The other half is conveying the research findings to the public and industries that have the wherewithal to take a project from ‘proof of concept’ to a ‘product’. It is they who bridge the gap between scientists and the common man.

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