Pharmacophore-Based Virtual Screening,Quantum Mechanics Calculations,and Molecular Dynamics Simulation Approaches Identified Potential Natural Antiviral Drug Candidates against MERS-CoV S1-NTD

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >−9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.     

Electronic properties of chalcopyrite CuAlX2(X=S,Se,Te) compounds

We present results of the band structure and density of states for the chalcopyrite compounds CuAlX₂ (X=S,Se,Te) using the state-of-the-art full potential linear augmented plane wave (FP-LAPW) method. Our calculations show that these compounds are direct band gap semiconductors. The energy gap decreases when S is replaced by Se and Se replaced by Te in agreement with the experimental data. The values of our calculated energy gaps are closer to the experimental data than the previous calculations. The electronic structure of the upper valence band is dominated by the Cu-d and X-p interactions. The existence of Cu-d states in the upper valence band has significant effect on the optical band gap.     

Experimental and theoretical investigations of the first and second order optical susceptibilities of BiB3O6 single crystal

The first and second order optical susceptibilities of BiB₃O₆ are calculated using the full potential linear augmented plane wave method. We find that BiB₃O₆ is a semiconductor with an indirect energy gap of 3.97 eV, to be compared to the experimental value of 4.55 eV. The calculations of the first order optical susceptibilities are compared with our measurements. We present results for the birefringence, and real and imaginary parts of the frequency dependent linear and nonlinear optical response. The calculated birefringence at zero energy is negative, in agreement with our experiments. We calculated and measured the refractive indices, and good agreement is found. Calculations are reported for the frequency dependent complex second order nonlinear optical susceptibilities χ_abc ⁽²⁾(ω). BiB₃O₆ exhibits a larger second harmonic generation efficiency than other known materials, such as lithium borate, KTiOPO₄, and BaB₂O₄. Our X-ray photoelectron spectroscopic (XPS) technique measured the concomitant photoemitted electrons with discrete kinetic energies that characterize the emitting atoms and their bonding states. Our XPS measurements show that the BiB₃O₆ structure contains parallel layers of six-fold coordinated Bi atoms alternating with borate layers, which are constituted by BO₄ tetrahedra and BO₃ triangles. PACS 71.15.Ap; 78.40.Fy; 78.20.Ci; 61.50.Ks; 71.15.Mb     

Effects of POSS nanoparticles on glass transition temperatures of ultrathin poly(t‐butyl acrylate) films and bulk blends

As a model system, thin films of trisilanolphenyl‐POSS (TPP) and two different number average molar mass (5 and 23 kg mol^?1) poly(t‐butyl acrylate) (PtBA) were prepared as blends by Langmuir–Blodgett film deposition. Films were characterized by ellipsometry. For comparison, bulk blends are prepared by solution casting and the samples are characterized via differential scanning calorimetry. The increase in T_g as a function of TPP content for bulk high and low molar mass samples are in the order of ～10 °C. Whereas bulk T_g shows comparable increases for both molar masses (～10 °C), the increase in surface T_g for higher molar mass PtBA is greater than for low molar mass (～22 °C vs. ～10 °C). Nonetheless, the total enhancement of T_g is complete by the time 20 wt % TPP is added without further benefit at higher nanofiller loads. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 175–182     

Synthesis and characterization of polybrominated fluorenes and their conversion to polyphenylated fluorenes and cyclopenta[def]triphenylene

We report the synthesis and characterization of polyphenylated fluorene derivatives and a ring cyclized product containing cyclopenta[def]triphenylene core. Polybromination on fluorene was achieved either by solid state reaction with bromine or utilizing Br₂/KBrO₃ in AcOH/H₂SO₄ mixture. The bromofluorenes were converted to the corresponding polyphenylated fluorenes by Suzuki coupling protocol. A hexabromofluorene underwent a multifold Suzuki coupling followed by C–H activation to produce a cyclopenta[def]triphenylene derivative. Fluorene ring showed a severe distortion from planarity beyond tetra-substitution which manifested in the optical properties.     

A note on the strong polynomiality of convex quadratic programming

We prove that a general convex quadratic program (QP) can be reduced to the problem of finding the nearest point on a simplicial cone inO(n ³ +n logL) steps, wheren andL are, respectively, the dimension and the encoding length of QP. The proof is quite simple and uses duality and repeated perturbation. The implication, however, is nontrivial since the problem of finding the nearest point on a simplicial cone has been considered a simpler problem to solve in the practical sense due to its special structure. Also we show that, theoretically, this reduction implies that (i) if an algorithm solves QP in a polynomial number of elementary arithmetic operations that is independent of the encoding length of data in the objective function then it can be used to solve QP in strongly polynomial time, and (ii) ifL is bounded by a first order exponential function ofn then (i) can be stated even in stronger terms: to solve QP in strongly polynomial time, it suffices to find an algorithm running in polynomial time that is independent of the encoding length of the quadratic term matrix or constraint matrix. Finally, based on these results, we propose a conjecture.corresponding author. The research was done when the author was at the Department of IE & OR, University of California at Berkeley, and partially supported by ONR grant N00014-91-j-1241.     

Reactions of the 2-cyano-2-propyl radical with vinyl acetate and other monomers: A study of head-addition

Polymers have been prepared at 60 and 100°C using initiators giving the 2-cyano-2-propyl radical enriched with carbon-13 in the nitrile group. Examination by NMR of the (CH₃)₂C(CN)? end groups in the resulting polymers of vinyl acetate (VAC) and of appropriate model compounds has indicated that up to 20% of these end groups correspond to the product of head-addition of the primary radical to VAC at 60°C. Similar end groups have been found in poly(vinyl formate) but not in poly(methyl methacrylate) and polystyrene. In polyVAC prepared at 100°C, the proportion of end groups attached to the head of a monomeric unit is higher than for polymers made at 60°C.