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

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

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

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 msm_s and ϵ′/ϵ\epsilon'/\epsilon 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 $\epsilon'/\epsilon$ 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 $U(1)_B$ model, consisting of a leptophobic $Z_B$ gauge boson, and an accompanying Higgs $S_B$. By requirement of anomaly cancellation, the fermion sector naturally contains a dark matter candidate---a Majorana isosinglet $\chi$ stabilized by an inherent $Z_2$ symmetry. The absence of evidence for $Z$ prime dijet resonances at the LHC suggests that the scale of symmetry breaking $\Lambda_{B}\gtrsim 500$ 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 $|\theta|\lesssim 0.22$. For small mixing angles of $|\theta| \lesssim 10^{-3}$, the $\mathcal{O}(10\%)$ branching fractions of the fermion loop-mediated $S_B\rightarrow\gamma \gamma$, $Z\gamma$, $ZZ$ 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