Significance The aggregation of the amyloid- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"><mml:mi>β</mml:mi></mml:math> peptide (A ) into neurotoxic oligomers is central to development Alzheimer’s disease. One possible source their toxicity results from interactions A with neuronal membrane, damaging membrane integrity and thus neurons. However, molecular details these are unclear. Here, we contrast dimerization in solution at membrane. Our clearly indicate that...

Abstract In comparing purified mouse olfactory sensory neurons (OSNs) with neighboring cells, we identified 54 differentially expressed transcripts. One‐third of the transcripts encode proteins no known function, but others have functions that correlate challenges faced by OSNs. The OSNs a diversity signaling protein genes, including stomatin (Epb7.2), S100A5, Ddit3, Sirt2, CD81, Sdc2, Omp, and Ptpla. elaboration dendrites, cilia, axons places in contact diverse cell types signals presumably...

In light of the high affinity Cu2+ for Alzheimer's Aβ1-42 and its ability to subsequently catalyze formation radicals, we examine effects binding, Aβ oxidation, an acidic environment on conformational dynamics smallest oligomer, dimer. Transition networks calculated from Hamiltonian replica exchange molecular (H-REMD) simulations reveal that decreased pH considerably increased β-sheet content, whereas binding exposed hydrophobic surface area, both which can contribute oligomerization...

To determine if (•)OH can initiate the unfolding of an amino acid residue, elementary reaction coordinates H abstraction by different conformations (β(L), γ(L), γ(D), α(L), and α(D)) Gly Ala dimethyl amides were computed using first-principles quantum computations. The MPWKCIS1K/6-311++G(3df,2p)//BHandHLYP/6-311+G(d,p) level theory was selected after combinations functionals basis sets compared. structures in steps compared to conformers Gly, Gly(•), Ala, Ala(•) absence (•)OH/H(2)O, which...

Abstract The effects on helical stability of weak polar interactions between aromatic side‐chains and the peptide backbone were examined. α‐Helical model peptides, hexa‐Ala, with sequential Tyr replacement, investigated computationally to obtain geometries energetics interactions. Geometries obtained B3LYP/6‐31G* level theory. Interaction energies calculated using BHandHLYP/cc‐pVTZ an improved method correct for basis set superposition error when fragmentation caused steric clashes. Both i ,...

Abstract Amyloid‐β (Aβ) is a natively unfolded peptide found in all Alzheimer's disease patients as the major component of fibrillar plaques, which are recognized an important pathological hallmark disease. The binding copper to Aβ increases its neurotoxicity, Cu 2+ causes become redox active and decreases lag time associated with aggregation. In addition, pH factor that influences both aggregation rates binding. Hamiltonian replica exchange molecular dynamics (H‐REMD) simulations enable...

In order to elucidate the mechanisms of radical-initiated unfolding a helix, thermodynamic functions hydrogen abstraction from C(α), C(β), and amide nitrogen Ala(3) in homopeptapeptide (N-Ac-AAAAA-NH(2); A5) by HO(•), HO(2)(•), O(2)(-•) were computed using B3LYP density functional. The functions, standard enthalpy (ΔH(o)), Gibbs free energy (ΔG(o)), entropy (ΔS(o)), reactants products these reactions with A5 3(10)-helical (A5(Hel)) fully extended (A5(Ext)) conformations at B3LYP/6-31G(d)...

The CH3 + HO2 reaction system was studied theoretically by a newly developed, HEAT345-(Q) method based CHEAT1 protocol and includes the combined singlet triplet potential energy surfaces. main simplification is on CCSDT(Q)/cc-pVDZ calculation which computationally inexpensive. Despite economic black-box treatment of higher excitations, results are within 0.6 kcal/mol highly accurate literature values. Furthermore, surpassed popular standard composite methods such as CBS-4M, CBS-QB3,...

Oxidative stress is known to play an important role in the pathogenesis of Alzheimer's disease. Moreover, it becoming increasingly evident that plasma membrane neurons plays a modulating aggregation and toxicity amyloid-β peptide (Aβ). In this study, combined interdependent effects oxidation interactions on 42 residues long Aβ isoform are investigated using molecular simulations. Hamiltonian replica exchange dynamics simulations utilized elucidate impact selected oxidized glycine Aβ42 with...

Polyurethanes (PUs) are widely used in different applications, and thus various synthetic procedures including one or more catalysts applied to prepare them. For PU foams, the most important nitrogen-containing compounds. Therefore, this work, catalytic effect of eight on urethane formation will be examined. The reactions phenyl isocyanate (PhNCO) methanol without presence have been studied discussed using G3MP2BHandHLYP composite method. solvent effects also considered by applying SMD...

Glycine (Gly) residues are particularly susceptible to hydrogen abstraction; which results in the formation of capto-dative stabilized Cα-centered Gly radical (GLR) on protein backbone. We examined effect GLR structure Trp cage; tryptophan zipper; and villin headpiece; three fast-folding stable miniproteins; using all-atom (OPLS-AA) molecular dynamics simulations. Radicalization changes conformation residue affects both neighboring but did not affect stability zipper. The helices away from...

The great physiological relevance of glycolipids is being increasingly recognized, and glycolipid interactions have been shown to be central cell-cell recognition, neuronal plasticity, protein-ligand other important processes. However, detailed molecular-level understanding these processes remains fully resolved. Molecular dynamics simulations could reveal the details interactions, but results may influenced by choice employed force field. Here, we compared behavior properties GM1, a common,...

Abstract On the basis of quantum chemical calculations C α ‐glycyl radical parameters have been developed for OPLS‐AA/L force field. The molecular mechanics hypersurface was fitted to calculated surface by minimizing their parameter dependent sum‐of‐squares deviations. To do this, a computer program in which energy derivatives with respect were analytically developed, implementing general method Lifson and Warshel (J Chem Phys 1968, 49, 5116) field optimization. This program, principle, can...

In this study, the thermodynamic functions of hydrogen abstraction from Cα and amide nitrogen Gly3 in a homo-pentapeptide (N-Ac–GGGGG–NH2; G5) by HO•, HO2•, O2−• were computed using Becke three-parameter Lee-Yang-Parr (B3LYP) density functional. The functions, standard enthalpy (ΔH°), Gibbs free energy (ΔG°), entropy (ΔS°), these reactions with G5 310-helical (G5Hel) fully-extended (G5Ext) conformations at B3LYP/6-31G(d) B3LYP/6-311+G(d,p) levels theory, both gas phase conductor-like...

The epimerization of amino acid residues increases with age in living organisms. In the present study, structural consequences and thermodynamic functions thymopentin (TP-5), active site thymic hormone thymopoietin, were studied using molecular dynamics density functional theory methods. results show that free radical-initiated D-amino formation is energetically favoured (−130 kJmol−1) for each residue induces significant changes to peptide structure. comparison wild-type (each...

Bursopentin (BP⁵, H-Cys¹-Lys²-Arg³-Val⁴-Tyr⁵-OH), found in the bursa Fabricius of chicken, is a pentapeptide that protects organism from oxidative stress by reducing intracellular generation reactive oxygen species.

A tremendous number of solvents, either as liquids or vapors, contaminate the environment on a daily basis worldwide. Olefin metathesis, which has been widely used high-yielding protocols for ring-opening metathesis polymerization (ROMP), ring-closing (RCM), and isomerization reactions, is typically performed in toxic volatile solvents such dichloromethane. In this study, results our systematic experiments with Grubbs G1, G2, Hoveyda-Grubbs HG2 catalysts proved that benzotrifluoride (BTF)...