Search
Now showing items 1-10 of 70
Mechanistic insights into protein stabilization and protein-protein interactions
Most amino acid substitutions in a protein either lead to partial loss of function or are near neutral. Several studies have shown the existence of second-site mutations that can rescue the defects caused by diverse loss ...
Probing Protein Sequence-Function Relationships using Deep Mutational Scanning
Deep Mutational Scanning (DMS) approaches help elucidate sequence-function-phenotype relationships in proteins, which ultimately improves our understanding of residue (or nucleotide)-specific contributions to protein ...
Structural and functional insights of biological macromolecules associated with infectious diseases – single particle cryo-electron microscopy based studies
In the global context, particularly in India, the two most important infectious diseases among many others are Tuberculosis (TB), an age-old disease and COVID-19, a new-age disease. This thesis focuses on some of the key ...
Structural, mechanistic and pharmacological studies of inhibitory neurotransmitter transporters
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). The synaptic levels of GABA are controlled by the activity of GABA transporters (GATs) present in the presynaptic ...
Structural and Biophysical studies to evaluate the influence of oligomerization on biomolecular function
Oligomeric proteins are more common than monomers. This aspect of molecular evolution substantially contributes to functional diversity and the acquisition of features such as cooperativity and regulatory mechanisms. Not ...
Homeostasis of cyclic-di-AMP in Mycobacterium smegmatis: Functional and structural contributions of c-di-AMP synthase (MsDisA) and hydrolase (MsPDE)
In bacteria, cyclic-di-nucleotide based second messengers regulate various physiological processes including the stress response. For the past decades, cyclic diadenosine monophosphate (c-di-AMP) has emerged as a crucial ...
Structural insights into assembly and regulation of HigBA toxin-antitoxin system from Escherichia coli
In the last few decades, bacterial Toxin-antitoxin (TA) systems have been identified to play crucial roles in bacterial survival under stressful conditions and virulence. TA systems are pair of genetic elements where one ...
Mutational sensitivity of CcdB mutants in their native operonic context
Determining the precise effects of thousands of point mutants on protein structure, stability, and activity is a challenging task. Chapter 1 introduces how next-generation sequencing technologies exploit phenotypic screens ...
Robustness of Neural Activity Dynamics in the Medial Entorhinal Cortex
Biological systems exhibit considerable heterogeneity in their constitutive components and encounter stochasticity across all scales of analysis. Therefore, central questions that span all biological systems are: (a) How ...
Insights into the conformational stability & pharmacology of peptides through side chain and backbone modification
The first part of the work presented in the thesis deals with CH-pi interaction, which is a lesser-known non-covalent interaction in proteins. We identified several CH-pi donor-acceptor pairs involving amino acids side ...