The association of the secondary DNA-binding site of linker histone H5 in a nucleosome

Bibliography: leaves 153-170.In order to understand the role of linker histones in the formation of the 30-run chromatin fibre as well as their role in transcriptional repression, it is essential to know their location on the nucleosome. In this study, we have modelled the location of the globular domain of chicken linker histone HS (GHS) on the nuc1eosome. The primary DNA binding site of GH5 was modelled by homology to the co-crystal structure of the E. coli CAP-DNA complex

The Effect of Geometrical Isomerism of 3,5-Dicaffeoylquinic Acid on Its Binding Affinity to HIV-Integrase Enzyme: A Molecular Docking Study

A potent plant-derived HIV-1 inhibitor, 3,5-dicaffeoylquinic acid (diCQA), has been shown to undergo isomerisation upon UV exposure where the naturally occurring 3trans,5trans-diCQA isomer gives rise to the 3cis,5trans-diCQA, 3trans,5cis-diCQA, and 3cis,5cis-diCQA isomers. In this study, inhibition of HIV-1 INT by UV-induced isomers was investigated using molecular docking methods. Here, density functional theory (DFT) models were used for geometry optimization of the 3,5-diCQA isomers. The YASARA and Autodock VINA software packages were then used to determine the binding interactions between the HIV-1 INT catalytic domain and the 3,5-diCQA isomers and the Discovery Studio suite was used to visualise the interactions between the isomers and the protein. The geometrical isomers of 3,5-diCQA were all found to bind to the catalytic core domain of the INT enzyme. Moreover, the cis geometrical isomers were found to interact with the metal cofactor of HIV-1INT, a phenomenon which has been linked to antiviral potency. Furthermore, the 3trans,5cis-diCQA isomer was also found to interact with both LYS156 and LYS159 which are important residues for viral DNA integration. The differences in binding modes of these naturally coexisting isomers may allow wider synergistic activity which may be beneficial in comparison to the activities of each individual isomer