Molecular modeling, dynamics simulation and characterization of human inositol hexakisphosphate kinase 1 (IP6K1) related to diabetes

Inositol hexakisphosphate kinase-1 (IP6K1) protein plays an important role in insulin signaling producing IP7 that inhibit the action of protein kinase B (Akt). Inhibition of IP6K1 has been proposed as a novel way to enhance insulin signaling. Characterization and binding interaction of IP6K1 is essential for rational anti-diabetic drug development targeting this protein. Computational tools were used to analyze the physicochemical characteristics of IP6K1. Homology modelling reliably predicts the tertiary structure of IP6K1. Derived three-dimensional models werethen used to predict the binding mode and interacting amino acid residues. MD simulation (30 ns) was employed to investigate the protein dynamics. The modeled IP6K1 exhibited secondary characteristics comprising of 63.3% helixes, 30.2% sheets and 13.4% turns with an aliphatic index of 65.83 and instability index 50.53 showing that the protein is relatively unstable without its appropriate environment. The extinction coefficient was 34560 while the grand average of hydropathicity was −0.724. Homology modelling was performed by SWISS-MODEL program and the proposed model was evaluated as reliable based on RAMPAGE’s Ramachandran plot, and ProSA analyses. RMSD, RMSF, Rg revealed that the protein attained stability around 20ns. This appeared to be the first attempt to portray molecular dynamic simulation of IP6K1 coupled with modeling and thorough characteristic analysis of the protein using parameters like Ramachandran plot, Chou and Fasman Secondary Structure prediction and Protparam. Studies like protein engineering, structure and function as well as activity analysis are suggested. Our computational studies reavealed the binding pocket and critical amino acid residues that can be exploited in the design of inhibitors of IP6K1 as antidiabetic drugs.Keywords: Insulin signaling, physicochemical characteristics, homology modelling, diabete

Gridless optical networking field trial: flexible spectrum switching, defragmentation and transport of 10G/40G/100G/555G over 620-km field fiber

We report the first gridless networking field trial with flexible spectrum switching nodes over 620 km field fibre links. Successful transport, spectrum switching and defragmentation achieved for mixed line signals including 555G and coherent 100G

Severe disruption and disorganization of dermal collagen fibrils in early striae gravidarum

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142909/1/bjd15895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142909/2/bjd15895_am.pd

Search for heavy resonances decaying to a top quark and a bottom quark in the lepton+jets final state in proton–proton collisions at 13 TeV

A search is presented for narrow heavy resonances decaying to a top quark and a bottom quark using data collected by the CMS experiment at √s = 13TeV in 2016. The data set analyzed corresponds to an integrated luminosity of 35.9 fb−1. Final states that include a single lepton (e, μ), multiple jets, and missing transverse momentum are analyzed. No evidence is found for the production of a W′ boson, and the production of right-handed W′ bosons is excluded at 95% confidence level for masses up to 3.6 TeV depending on the scenario considered. Exclusion limits for W′ bosons are also presented as a function of their coupling strength to left- and right-handed fermions. These limits on a W′ boson decaying via a top and a bottom quark are the most stringent published to date

Measurement of angular parameters from the decay B⁰ → K⁎0^{⁎0} μ⁺ μ⁻ in proton–proton collisions at √s 8 TeV

Angular distributions of the decay B⁰  → K$^{⁎0}$ μ⁺ μ⁻ are studied using a sample of proton–proton collisions at √s=8TeV collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 20.5fb⁻¹ . An angular analysis is performed to determine the P₁ and P$^{\u27}$₅ parameters, where the P$^{\u27}$₅ parameter is of particular interest because of recent measurements that indicate a potential discrepancy with the standard model predictions. Based on a sample of 1397 signal events, the P₁ and P$^{\u27}$₅ parameters are determined as a function of the dimuon invariant mass squared. The measurements are in agreement with predictions based on the standard model