The Experts below are selected from a list of 19413 Experts worldwide ranked by ideXlab platform
Barak Akabayov - One of the best experts on this subject based on the ideXlab platform.
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identification of dna primase inhibitors via a Combined Fragment based and virtual screening
Scientific Reports, 2016Co-Authors: Stefan Ilic, Sabine R Akabayov, Gerhard Wagner, Haribabu Arthanari, C Richardson, Barak AkabayovAbstract:The structural differences between bacterial and human primases render the former an excellent target for drug design. Here we describe a technique for selecting small molecule inhibitors of the activity of T7 DNA primase, an ideal model for bacterial primases due to their common structural and functional features. Using NMR screening, Fragment molecules that bind T7 primase were identified and then exploited in virtual filtration to select larger molecules from the ZINC database. The molecules were docked to the primase active site using the available primase crystal structure and ranked based on their predicted binding energies to identify the best candidates for functional and structural investigations. Biochemical assays revealed that some of the molecules inhibit T7 primase-dependent DNA replication. The binding mechanism was delineated via NMR spectroscopy. Our approach, which combines Fragment based and virtual screening, is rapid and cost effective and can be applied to other targets.
Sabine R Akabayov - One of the best experts on this subject based on the ideXlab platform.
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identification of dna primase inhibitors via a Combined Fragment based and virtual screening
Scientific Reports, 2016Co-Authors: Stefan Ilic, Sabine R Akabayov, Gerhard Wagner, Haribabu Arthanari, C Richardson, Barak AkabayovAbstract:The structural differences between bacterial and human primases render the former an excellent target for drug design. Here we describe a technique for selecting small molecule inhibitors of the activity of T7 DNA primase, an ideal model for bacterial primases due to their common structural and functional features. Using NMR screening, Fragment molecules that bind T7 primase were identified and then exploited in virtual filtration to select larger molecules from the ZINC database. The molecules were docked to the primase active site using the available primase crystal structure and ranked based on their predicted binding energies to identify the best candidates for functional and structural investigations. Biochemical assays revealed that some of the molecules inhibit T7 primase-dependent DNA replication. The binding mechanism was delineated via NMR spectroscopy. Our approach, which combines Fragment based and virtual screening, is rapid and cost effective and can be applied to other targets.
Steven M Goodman - One of the best experts on this subject based on the ideXlab platform.
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genetic population structure in the boky boky carnivora eupleridae a conservation flagship species in the dry deciduous forests of central western madagascar
Animal Conservation, 2012Co-Authors: Jansen B Van Vuuren, L Woolaver, Steven M GoodmanAbstract:The boky-boky, Mungotictis decemlineata, is an endemic and presumed forest-dependent carnivoran species restricted to lowland central western Madagascar. It inhabits dry deciduous forests, which have been severely reduced in surface area with ∼60% destroyed or degraded by humans during the past 60 years. M. decemlineata is limited to the remnant forests of the central and southern Menabe, and using samples collected from sites across this zone, a phylogeographic study was conducted based on two mitochondrial (1140 base pairs [bp] of cytochrome b and 563 bp of the control region) and one nuclear Fragment (591 bp of the seventh intron of the fibrinogen gene). Forty-seven individuals were included from the central Menabe from four principal localities and two animals from the southern Menabe from a single locality. Low sequence divergence (1.65% for the Combined Fragment, 4.26% for the control region and 0.78% for cytochrome b) characterized specimens across a zone of 130 km delimited by the Tsiribihina River to the north and the Mangoky River to the south; this area includes most of the geographical range of M. decemlineata. Phylogenetic trees, haplotype networks and exact test of population differentiation did not reveal any meaningful geographic partitioning of genetic variation. However, shallow yet significant genetic structure was revealed by ΦST calculations for the Combined as well as separate DNA Fragments, which we ascribe to isolation-by-distance. We proposed two different scenarios to explain the lack of meaningful phylogeographical structure in Mungotictis: (1) for this forest-dependent species, dispersal during periods of more continuous forest cover gave rise to a genetic meta-population or (2) that it is able to cross non-forested zones and broadly disperses, leading to high levels of genetic homogeneity. Current inferences favour the first hypothesis. The short- and medium-term future of this taxon is in jeopardy associated with habitat destruction across its geographical range.
Stefan Ilic - One of the best experts on this subject based on the ideXlab platform.
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identification of dna primase inhibitors via a Combined Fragment based and virtual screening
Scientific Reports, 2016Co-Authors: Stefan Ilic, Sabine R Akabayov, Gerhard Wagner, Haribabu Arthanari, C Richardson, Barak AkabayovAbstract:The structural differences between bacterial and human primases render the former an excellent target for drug design. Here we describe a technique for selecting small molecule inhibitors of the activity of T7 DNA primase, an ideal model for bacterial primases due to their common structural and functional features. Using NMR screening, Fragment molecules that bind T7 primase were identified and then exploited in virtual filtration to select larger molecules from the ZINC database. The molecules were docked to the primase active site using the available primase crystal structure and ranked based on their predicted binding energies to identify the best candidates for functional and structural investigations. Biochemical assays revealed that some of the molecules inhibit T7 primase-dependent DNA replication. The binding mechanism was delineated via NMR spectroscopy. Our approach, which combines Fragment based and virtual screening, is rapid and cost effective and can be applied to other targets.
Jansen B Van Vuuren - One of the best experts on this subject based on the ideXlab platform.
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genetic population structure in the boky boky carnivora eupleridae a conservation flagship species in the dry deciduous forests of central western madagascar
Animal Conservation, 2012Co-Authors: Jansen B Van Vuuren, L Woolaver, Steven M GoodmanAbstract:The boky-boky, Mungotictis decemlineata, is an endemic and presumed forest-dependent carnivoran species restricted to lowland central western Madagascar. It inhabits dry deciduous forests, which have been severely reduced in surface area with ∼60% destroyed or degraded by humans during the past 60 years. M. decemlineata is limited to the remnant forests of the central and southern Menabe, and using samples collected from sites across this zone, a phylogeographic study was conducted based on two mitochondrial (1140 base pairs [bp] of cytochrome b and 563 bp of the control region) and one nuclear Fragment (591 bp of the seventh intron of the fibrinogen gene). Forty-seven individuals were included from the central Menabe from four principal localities and two animals from the southern Menabe from a single locality. Low sequence divergence (1.65% for the Combined Fragment, 4.26% for the control region and 0.78% for cytochrome b) characterized specimens across a zone of 130 km delimited by the Tsiribihina River to the north and the Mangoky River to the south; this area includes most of the geographical range of M. decemlineata. Phylogenetic trees, haplotype networks and exact test of population differentiation did not reveal any meaningful geographic partitioning of genetic variation. However, shallow yet significant genetic structure was revealed by ΦST calculations for the Combined as well as separate DNA Fragments, which we ascribe to isolation-by-distance. We proposed two different scenarios to explain the lack of meaningful phylogeographical structure in Mungotictis: (1) for this forest-dependent species, dispersal during periods of more continuous forest cover gave rise to a genetic meta-population or (2) that it is able to cross non-forested zones and broadly disperses, leading to high levels of genetic homogeneity. Current inferences favour the first hypothesis. The short- and medium-term future of this taxon is in jeopardy associated with habitat destruction across its geographical range.