Structural Biology and Biocomputing

Research Group

K. Sekar

Computational and Data Sciences, IISc

Proteins are large, complex molecules that play many critical roles in the body. They perform most of the functions in cells and are required for the regulation of the body’s tissues and organs. Enzymes are indispensable biological molecules that are vital for a wide variety of functions in living organisms. More specifically enzymes are biological macromolecules that catalyze chemical reactions. Enzymes are essential to determine the metabolic pathways that occur in the cells present in our body and catalyze several biochemical reactions. Although enzymes are usually large globular protein molecules, only a part of it is involved in its catalytic functionality. The active site (catalytic site + binding site) of the enzyme is specific to its function as only a substrate with the particular shape will fit into it. The enzyme-substrate binding is like that of a lock and key.

Proteins are made up of hundreds or thousands of amino acids, which are attached linearly. These twenty different types of amino acids are combined to make a protein. The amino acid sequence helps in determining unique three-dimensional structure and its biological function. Mostly enzymes are proteins whose function is determined by their unique three-dimensional structure. The three-dimensional structure of an enzyme plays a major role in determining the function of its active site and any change in the amino acid sequence could result in a change of its three dimensional structure and function.

Structural biology studies the biochemical and biophysical characteristics of protein structures after elucidating the three-dimensional structure. The three-dimensional structure of proteins is determined, mainly, using X-ray crystallography. The atomic coordinates of the protein reveal the molecular basis behind the protein’s function. The detailed analysis of the three-dimensional structure of proteins facilitates the understanding of various structural and functional roles and significance of the proteins. Such analyses provide us a wealth of knowledge and open up avenues for further exploration of cellular machinery functions, like the viral or bacterial disease cycles. This is especially relevant and prevalent in drug designing which extensively depends and relies on the three dimensional structure of the enzyme.

Thus, my group is interested in solving three-dimensional protein structures, in particular enzymes, using X-ray crystallography. Further, we also design suitable inhibitors for these enzymes. In addition, my group performs molecular dynamics simulations to better understand the structure, function and relationship of these macromolecules.