Carried out drug design project aimed at designing novel dimethyl-amino-ethyl-acridine-carboxamide analogues which has optimal thermodynamic properties with good binding to specialized DNA structures, collaboratively with the NMR group of University of Southern Denmark, Odense. Extensive molecular dynamics simulations were carried out to study the drug induced conformational perturbations in the DNA structures and the movements (positions) of flipped adenine bases whose molecular density were missing in the crystal diffraction maps. The reason for missing densities are due to high thermal motions of the flipped bases and thus could only be studied computationally. All computations were perfomed in the Horse Shoe Super Computer.

July 2008 – September 2008

Our research group have been cultivating knowledge in the DNA Holliday junctions and DNA G-Quadruplex structures over the past decade and thus it was the main part of my PhD thesis. The research was focussed on the theme : "Design of DACA Analogues for Novel Anti-Cancer Mechanisms". As obvious from the tile, our group was mainly involved in optimizing, designing & developing novel DACA class (mixed topo-isomerase poisons) of minor groove intercalators. The crystal structures revealing DNA Holliday Junction - apo structure and the influence of different mono-valent and di-valent cations were previously established by our group. Upon gaining knowledge about the target chemistry, further work followed on recognition of the target by small molecules. One of such attempts revealed that dimethyl-aminoethyl-carboxamide derivative containing a hexa-methyl linker could infact recognize the DNA HJ and threw light on a unique symmetrical adenine flip-out mechanism of drug binding in the core of the DNA Holliday junction.But, this linker length was later considered as non-specificity linker because it recognized two independent DNA duplexes instead of a HJ, in a later study. In order to understand the role of different linker lengths in recognizing the DNA HJ at the atomic level, detailed molecular dynmaics (parm99SB force field) and molecular docking studies (both MM and QM/MM docking techniques with OPLS force field and DFT - B3LYP with 6-31G* basis sets) were conducted and a solution about a more better linker length was suggested.

Conducted several research projects in bioinformatics and lectured an introductory bioinformatics course to final year B.Tech. Information Technology students.

Achievements:

1. 99% pass rate (in 2004) of my students in the Anna University (state level) examination.
2. Listed in the Top 10 Best Lecturers of the college.
3. Awarded a golden bracelet for achieving high student success ratio in examinations.