60,891 research outputs found
Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors.
The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to 10.3 kcal/mol. The highest affinity molecules were found to interact with conserved residues including Gln138, Gly222, Ile529, Asn540 and Thr530. A library containing 1738 FDA approved drugs were screened additionally and revealed Paliperidone as a top hit with a binding affinity of -10 kcal/mol. Predicted ligands are ideal leads for new antivirals as they were targeted to evolutionary conserved binding sites
Influenza A nucleoprotein binding sites for antivirals: current research and future potential
This document is the Accepted Manuscript version of the following article: Andreas Kukol and Hershna Patel, ‘Influenza A nucleoprotein binding sites for antivirals: current research and future potential’, Future Biology, Vol 9(7): 625-627, July 2014. The version of record is available online at doi: 10.2217/fvl.14.45Peer reviewedFinal Accepted Versio
Evaluation of a novel virtual screening strategy using receptor decoy binding sites
Virtual screening is used in biomedical research to predict the binding affinity of a large set of small organic molecules to protein receptor targets. This report shows the development and evaluation of a novel yet straightforward attempt to improve this ranking in receptor-based molecular docking using a receptor-decoy strategy. This strategy includes defining a decoy binding site on the receptor and adjusting the ranking of the true binding-site virtual screen based on the decoy-site screen. The results show that by docking against a receptor-decoy site with Autodock Vina, improved Receiver Operator Characteristic Enrichment (ROCE) was achieved for 5 out of fifteen receptor targets investigated, when up to 15 % of a decoy site rank list was considered. No improved enrichment was seen for 7 targets, while for 3 targets the ROCE was reduced. The extent to which this strategy can effectively improve ligand prediction is dependent on the target receptor investigated
Package-X: A Mathematica package for the analytic calculation of one-loop integrals
Package-X, a Mathematica package for the analytic computation of one-loop
integrals dimensionally regulated near 4 spacetime dimensions is described.
Package-X computes arbitrarily high rank tensor integrals with up to three
propagators, and gives compact expressions of UV divergent, IR divergent, and
finite parts for any kinematic configuration involving real-valued external
invariants and internal masses. Output expressions can be readily evaluated
numerically and manipulated symbolically with built-in Mathematica functions.
Emphasis is on evaluation speed, on readability of results, and especially on
user-friendliness. Also included is a routine to compute traces of products of
Dirac matrices, and a collection of projectors to facilitate the computation of
fermion form factors at one-loop. The package is intended to be used both as a
research tool and as an educational tool.Comment: Package files are available at http://packagex.hepforge.or
Constraints on and from Lattice QCD
Results for light quark masses obtained from lattice QCD simulations are
compared and contrasted with other determinations. Relevance of these results
to estimates of is discussed.Comment: Latex, 7 pages, 2 figures. Invited talk presented at the Workshop on
High Energy Physics Phenomenology ``WHEPP-6'', 3-15 January 2000, Institute
of Mathematical Sciences, Chennai, India. To appear in the proceeding
An application of statistics in mixture of exponential distributions
Order statistics in application to exponential distribution
Leptobaryons as Majorana Dark Matter
We explore the dark matter and collider phenomenology of the minimal gauged
model, consisting of a leptophobic gauge boson, and an
accompanying Higgs . By requirement of anomaly cancellation, the fermion
sector naturally contains a dark matter candidate---a Majorana isosinglet
stabilized by an inherent symmetry. The absence of evidence for
prime dijet resonances at the LHC suggests that the scale of symmetry
breaking GeV. Saturation of dark matter abundance
together with limits on the direct detection cross section (dominated by Higgs
exchange) constrains the Higgs mixing angle to . For
small mixing angles of , the
branching fractions of the fermion loop-mediated ,
, modes may provide clues about the fermion content of the model
at the LHC.Comment: 15 pages, 10 figures; v3: corrected typos, to appear in PR
The Electroweak Vacuum Angle
We reveal a new source of CP-violation in the electroweak sector that is free
of any experimental bounds, and we highlight the possible implications for
baryogenesis.Comment: to appear in Physics Letters
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