|Dr.Dhaval Patel||Group Leader|
|Current Research Students|
Our current research primarily aims to explore the connection between the structures and functions of proteins. The genome projects in current era yielded the sequences of thousands of proteins. Elucidating the roles these proteins play in health and disease, and also how they can be used and/or modified for the development of novel therapeutics, will be aided by a better understanding of how a protein's amino acid sequence determines its structure and ultimately how a structure determine protein's function. We are also interested to explore the kinetics and dynamics of protein structure in lieu of events such as ligand binding. We aim to use different interdisciplinary techniques at the interface of biochemistry, biophysics and computational biology along with X-ray crystallography & structural studies in several projects to study the connection between protein sequences, structures, and functions. We hope that our research will play a key role in scientific and technological advancements along with the generation of new knowledge towards research, education, and training. .
Due to recent technological advancements, protein function determination from known functions of homologous proteins has become an easier task, though this can be complicated in case of increasing reports of "moonlighting proteins". Moonlighting proteins are multifunctional proteins that have more than once unrelated function where the multiple functions are not a result of splice variants, gene fusions, or multiple isoforms. The outcome of exploring moonlighting proteins could help in prediction which additional proteins might also have a second function, which would be useful in predicting functions(s) of new proteins identified through genome projects and protein structure consortiums. Earlier, we had identified the molecular basis for moonlighting in GAPDH protein from Lactobacillus acidophilus and proposed that the carbohydrates in the gut presented on mucin are key interacting molecules with the protein (Patel et al., 2016). We hypothesize that the presence of unique signature sequences as well as an abundance of positive charge residues on the surface which is not present in non-moonlighting GAPDHs plays a significant role in GAPDH for adhesion to gut mucin. We aim to expand this study to pathogenic proteins so that the molecular basis can be explored in previously unidentified function and be used in the development of therapeutic interventions.
Antibiotic resistance is a serious and growing problem in India and around the world. The WHO describes it as “one of the biggest threats to global health, food security, and development today” (who.int). As more and more bacteria develop antibiotic resistance, it leads to higher costs to treat infections and increased mortality. New types of antibiotics are needed which can be aided by the identification of novel proteins in pathogens that can be targeted to disrupt infection and virulence. Our objective is to gain insights into the structures and functions of proteins in bacterial pathogens as novel targets and further identify novel small molecule which can be developed as lead molecules. We aim to use high-throughput virtual screening using molecular docking approach, assisted by molecular dynamics simulations to identified lead compounds. Further, the protein-inhibitor interaction can be quantified using biophysical approaches and structural studies to gain insights into molecular recognition.