Showing papers in "Journal of the Indian Institute of Science in 2008"

Medical biofilms – Its formation and prevention using organic molecules

Abstract: Biofilms play a significant role in the area of clinical medicine. Currently research is in progress to understand their formation with a view to develop preventive measures to fight the infections caused due to biofilms that are formed on implanted medical devices. The determination of biofilm architecture, particularly the spatial arrangement of micro colonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Moreover, standard antimicrobial treatment fails to eradicate biofilms, due to the organisms adaptive resistance towards antibiotics. The need of the hour is the development of antimicrobial molecules or various combination techniques to counter biofilm infections. This review explains the mechanism of biofilm development and the reasons for its resistance to antimicrobial agents. Also various possible preventive measures, in particular development of anti microbial small molecules, are also discussed.

Advances in the Mathematical Modelling of Hepatitis C Virus Dynamics

Abstract: Mathematical models have provided key insights into the pathogenesis of hepatitis C virus (HCV) in vivo, suggested predominant mechanism(s) of drug action, explained confounding patterns of viral load changes in HCV infected patients undergoing therapy, and presented a framework for therapy optimization. In this article, I present an overview of the major advances in the mathematical modeling of HCV dynamics.

Crystal engineering with sterically-hindered molecular modules: unique supramolecular synthons and novel molecular self assembly

Abstract: The influence of sterics on the manifestation of supposedly robust supramolecular synthons has been examined in rationally designed molecular modules to afford novel insights as to the molecular self-assembly in the solid state. It is shown that novel molecular modules created by incorporating steric factors can be exploited to engineer porous crystals, which are sustained by hydrogen bonds and metal-ligand coordination bonds.

Structural variations in Z-DNA

Abstract: The first crystal structure of Z-DNA, i.e. of the sequence d(CGCGCG)2 established many sequence-dependent micro- structural features. Nevertheless, a regular model of Z-DNA could be built for alternating pyrimidine-purine sequences, with a dinucleotide duplex as the repeating unit, rather than the mononucleotide used in regular models of A and B type helices. In our laboratory, we have made systematic crystallographic studies to explore the precise influence of sequence on the microstructure of Z-DNA, especially the effect of the introduction of A.T base pairs in sequences that otherwise consisted of C.G base pairs. Using chiefly the technique of X-ray crystallography, we studied the following sequences: d(CACGCG).d(CGCGTG), d(CGCACG).d(CGTGCG), d(CACGCG).d(CGCGTG), d(CCCGGG)2, d(CGCGCA).d(TGCGCG), d(CGCGTACGCG)2, and d(CGCGCGTACGCGCG)2. These sequences were studied under various conditions of salt, pH, temperature, etc. Some of the results we obtained from these studies may be summarized as follows. Firstly, we observe sequence-dependent structural micro-heterogeneities in Z-DNA, which are correlated with the extent of the stretch of G.C base pairs, as well as with the degree and nature of the pyrimidine-purine alternation in the sequence. Secondly, the Z-DNA helices, which may be approximated to solid cylinders, achieve the closest packing in the crystals in the following manner. The cylinders are stacked on top of each other to form long infinite, pseudo-continuous columns, which are then bundled together in a hexagonal close packing arrangement. This packing motif is common to almost all the Z type structures that have been studied, both in our laboratory as well as elsewhere. Despite this common packing principle, it is possible to index the crystals in several different crystals systems and space groups, sometimes in a degenerate manner. The differences arise due to the alignment between adjacent columns. Also if the sequences are non-self complementary, like many of those above, the helical columns can point ‘up’ or ‘down’ and this allows an extra degree of freedom in choice of crystal system and space group. The third set of results obtained from these studies pertains to the interactions of various metal ions with the helices. We find, in particular, that cobalt and ruthenium hexammine ions perturb the tautomeric state of the adenine and thymine bases, leading to changes in the base pairing schemes.