Research Interests
Broadly my research interest is in the area of understanding the structure
and folding of proteins/polypeptides and their physical interactions principles, having therapeutic uses and their relationships with other biological systems like DNA, RNA and lipids.
1. "Homochiral Stereochemistry: The Missing Link of Structure to Energetics in Protein Folding."
Anil Kumar, Vibin Ramakrishnan, Ranjit Ranbhor, Kirti Patel and Susheel Durani
Journal of Physical Chemistry B, 2009, 113, 16435-16442.
The notion is tested that homochiral stereochemistry being ubiquitous to protein structure could be critical to protein folding as well, causing it to become frustrated energetically providing the basis for its solvent- and sequence-mediated control. The proof in support of the notion is found in a consensus of experiment and computation according to which suitable oligopeptides are in their folding-unfolding equilibria, at both macrostate and microstate levels, susceptible to dielectric because of the conflict of peptide-chain electrostatics with interpeptide hydrogen bonds when the structure is poly-L but not when it is alternating-L,D. The argument is thus made that homochiral stereochemistry may in protein folding provide the unifying basis for its solvent and sequence-mediated control based on screening of peptide-chain electrostatics under conflict with folding of the chain due to homochiral stereochemistry. Dielectric is brought into spotlight as the effect comparatively obscure but presumably critical to the folding in protein structure for its control.
2. "Homochiral Stereochemistry and Protein. Folding: Topological Blocks of Folding Path may manifest Φ,Ψ Dispersal under effect of poly-L Structure."
Anil Kumar, Buhpesh Goyal, Vibin Ramkrishnan, Ranjit Ranbhor, Kirti Patel, Kinshuk Raj Srivastava, Pooja Gupta and Susheel Durani 2011 (Under Review).
Is contact order-correlated kinetics, as two state thermodynamics, of protein folding an effect of homochiral structure stereochemical in the basis? We found the chain of peptides in an appropriate model fold from having f,ys localized in methanol to having them dispersed in water, and from having electrostatics minimized over the sequence-neighboring peptides in methanol to having it minimized over the sequence-non-neighboring peptides in water, and when the structure was homochiral, but not when it was heterochiral, being in the latter structure, irrespective of solvent, folded with f,ys localized and electrostatics minimized over the peptides both sequence neighboring and non-neighboring. To now assess if dispersal of f,ys might also affect folding kinetics, we study the octa-alanine model Ac-Ala8-NHMe for effect of having it mutated from homochiral, poly-L, to heterochiral, alternating-L,D, stereochemistry. Modeling equilibria with molecular dynamics in methanol and water as the solvents, and analyzing folding in molecular-structural detail, we find poly-L stereochemistry block pathways to dampen kinetics with locally-hydrogen-bonded folds dispersed in f,ys. Illuminating mechanism, the study establishes that homochiral stereochemistry could in the folding of protein-polypeptide-chain structure provide the basis for not only two-state thermodynamics but also topologically-dampened kinetics.
3. Stereochemical Design of "Paper-Clip" with L- and D-a- Amino-Acid Alphabet and its Serendipitous Assembly as a Nanotube.
Anil Kumar, Punam Ghosh, Kirti Patel and Susheel Durani 2011 (Manuscript under preparation).
4. IDeAS: Inverse Design Software for Mixed-L,D Proteins to Apply Side Chains in the Chirality of Interest
Ranjit Ranbhor, Abhijit Tendulkar, Anil Kumar, Vibin Ramkrishnan, Kirti Patel, Kinshuk Raj Srivastava and Susheel Durani Proteins: Structure, Function, and Bioinformatics, 2011 (Under Review).
Practically limitless in sequence diversity over side chains, protein-polypeptide structure is in folds, and thus in shapes of molecular folds, limited to only what is but possible for poly-L, i.e., homochiral, stereoisomer structure. To have shapes diversified to the unexplored possibilities of the folds of heterochiral structure, we introduced L- and D-α-amino acids as the alphabet, in polypeptide structure, of not only the chemical but also the stereochemical possibilities (Accounts of Chemical Research, 41, 1301-1308, 2008). To have stereochemically defined heterochiral folds tuned as proteins, we now present inverse-design software IDeAS to allow in application of side chains the chiral option of interest. Thus retrofitting side chains in L or D option, the software is shown to provide acceptable sequence solutions against stereochemically diverse folds and possible external ligands, including copies of the same fold, to achieve binding site for a non-protein ligand or for another protein, as a tertiary structure or an oligomer cyclic in symmetry. The attachment chirality in addition to the chemical detail in side chain as the programming variable allows the possibility of having protein structure designed not only chemically over side chains but also stereochemically in main chain.