"Basically, I'm not interested in doing research and I never have been. I'm interested in understanding, which is quite a different thing." - DAVID BLACKWELL -
Ultrafast Photochemistry and Photophysics Ultrashort laser pulses selectively trigger reaction both in energy and in time which means a redistribution of charge in the absorbing atom or molecule. While this redistribution modifies the field of forces within the molecule and leads to its transformation (e.g. via bond breaking, isomerisation, etc.), it also changes the field of forces between the excited molecule and the solvent species, forcing the latter to rearrange on a time scale that may be shorter or concurrent with that of intramolecular reorganisation. However, if photochemistry occurs on a timescale similar to internal conversion from upper excited states, vibrational or solvent relaxation, the conventional rules of photochemistry (Kasha's and Vavilov's rules) are no longer valid and the photochemistry may for example occur from upper excited states or before the lowest excited state has reached thermal equilibrium. Therefore excited state processes (vibrational relaxation, electron transfer, proton transfer, energy transfer, isomerization etc.) in neat solvents, solvents mixture and restricted/confined microenvironments are of particular interest from both chemical and biological perspectives.
Study of the Interfacial and Confined Water Water in nature is often located at an interface or confined within a small region, a few nanometres in size. The properties and dynamics of water are changed near the interfaces and in the confined environments. Self-organized molecular assemblies such as micelles and vesicles in water, reverse micelles and microemulsions in hydrocarbons, supramolecules involving cage-like hosts (e.g., cyclodextrins or calixarenes), microporous solids (e.g., zeolites), semirigid materials (e.g., polymers, hydrogels, etc.) and so on provide a fascinating world of bio-mimicking systems. Near charges or interfaces, the properties and dynamics of water cannot be extrapolated from those of bulk water and need to be examined and compared to the dynamical properties of bulk water.
Effect of Osmolytes and Crowding Agents Under environmental stress such as potentially harmful fluctuations in temperature, pressure and solution composition, most organisms have adapted to deal with issues of intracellular protein stability and solubility by production and accumulation of certain classes of small organic molecules. Most of these compounds are not only commonly available but have been used in protein crystallization cocktails. These osmolytes are typically accumulated in the intracellular environment at relatively high concentrations e.g., urea concentration may reach 5.4 M in water-independent desert rodents, whereas up to 3 M is more normal for water-dependent rodents. It is extremely important to understand the underlying mechanisms of how they stabilize (or destabilize) proteins/ enzymes in a living organism. Do they induce a structural modification of water or act directly on proteins? If they do modulate the properties of water molecules, does the presence of multiple H-bond donor and/or acceptor sites (OH or HN) in osmolytes play a critical role? Moreover, most of the studies are done in dilute solutions. However, real biological environment differs from the idealized solvent bath in two important aspects. Firstly, a biological medium is likely to contain a high total concentration of nominally soluble macromolecules, even with a single species present at a predominantly high concentration. More commonly, a medium generally contains variety of macromolecular species collectively occupying a substantial fraction of the total volume of it. Such media are commonly referred to as “crowded” rather than “concentrated”. The second aspect is “confinement” which refers to situations in which macromolecules find themselves inside small compartments. Therefore, it becomes essential to undertake standard biophysical studies on protein solutions in such environments (confined and crowded) rather in a bulk phase.
Biomolecule-ligand Interactions The correlation between structure and function of biomolecules is a long-standing problem in biology. Structurally similar biomolecules exhibit differences in function e.g, both trypsin and chymotrypsin are hydrolytic in nature having similar structure but very different substrate specificities: trypsin hydrolyzes peptides with arginine or lysine residues, while chymotrypsin prefers peptides with large hydrophobic residue. The correlation between structure and function can be attributed to molecular recognition of small ligands/drugs by biological macromolecules. Since substrate specificity of biomolecules is crucial for almost every biological function, the exploration of the origin of substrate specificity has due importance for the design of molecules that could mimic the naturally occurring substrates or inhibit the activity of the concerned biomolecule.
Nano-bio Interactions Biological systems form sophisticated mesoscopic and macroscopic structures with tremendous control over the placement of nanoscopic building blocks within extended architectures. Both biological and nanoscale science meet at the same length scale because biomolecular components have typical size dimensions in the range of about 2–100 nm. In this regard, synthesis of bioconjugate nanomaterials using biological macromolecules has recently aroused great interest due to the broad range of applications of such hybrid materials, from life sciences to materials and nanoscience. The motivation is based on the unique properties of nanomaterials possessing strongly size-dependent optical, electrical, magnetic, and electrochemical properties combined with the perfect binding and biochemical functionality of biomacromolecules. The question that arises, do the biomolecules retain their structural and functional integrity after such modification? How do the bioconjugates can help to understand biological process like folding/unfolding, ligand binding etc.?