Biennial Report 2005-2007 - Saha Institute of Nuclear Physics

Biophysical Sciences 213pairs, formed through hydrogen bonds between complementary bases Adenine-Uracil and Guanine-Cytosine. Such A form helices are an important structural motif in RNA. It has been reportedearlier that apart from Watson-Crick edge, a base in RNA can also undergo pairing through Hoogsteenor the sugar edges. However, their role in a double helical region is not yet known. We havefirst detected all possible canonical or non-canonical base pairs from 208 high-resolution crystalstructures of RNA. Analysis of the surrounding regions of the non-canonical base pairs indicatesthat often these are located within double helical structures flanked by Watson-Crick base pairs.We have selected four such structures, which are 7-11 base pair long and carried out MolecularDynamics simulation. These models were neutralized, solvated by TIP3P water model and energyminimized prior to MD simulation. We found two of these short sequences undergo double helixmelting through breaking of base pairing, especially at the ends. One structure, which has threeconsecutive non-canonical base pairs, namely A:A S:H T, A:U H:W T and A:G H:S T base pairs,is found to be quite stable even after 3.0ns of MD simulation. This indicates such unusual basepairs can also lead to sufficient stability to the double helix formation.Somdutta Saha†, Parijat Majumder, Dhananjay BhattacharyyaBP6.1.3.9 Role of Base Pairs Flexibility in Molecular Recognition in a Protein/DNAComplexIn the indirect mode of protein/DNA recognition, substantial deformation of DNA is observedto form adequate number of non-covalent bonds. It is extremely important to know the role ofindividual base pair (bp) to have a microscopic picture of molecular recognition. We developeda semi-coarse grained approach using the crystal structure data to estimate the contribution ofdifferent bp steps in a protein-DNA complex. We calculate equilibrium properties and the kineticsof a protein/DNA complex via the binding patterns and the free energy profiles of the DNA bp step,obtained from their atomic configurations. We apply the method to the TATA-box binding protein(TBP)-TATA box DNA sequence complex. The local rigidity and time period of small oscillationscorresponding to each of the six local bp step motions are calculated from the curvature at freeenergy minimum of the free energy profile. We estimate the change in free energy and entropy foreach of the bp steps. We also estimate the free energy gain to the protein due to non-covalent bondformation with a particular bp step. The free energy barriers, experienced by the DNA bp steps intransition from the free state to the complexed state, along with the correlation between differentbp step parameters, suggest a multi step kinetics of the complexation.Sudipta Samanta†, Dhananjay Bhattacharyya, J Chakrabarti†BP6.1.4 Chemical Biology6.1.4.1 Zn(II)-containing enzymes as targets for DNA-binding aureolic acid group ofantibioticsMithramycin and chromomycin A3 are known to act via reversible association with DNA. In thelast few years, we have shown that metalloenzymes containing Zn(II) could be potential targetin vivo, because the antibiotics bind to Zn(II) with a high affinity. Our studies using alcoholdehydrogenase as a typical example have shown that the antibiotics bind to the metal ion at the