Parameters for Martini sterols and hopanoids based on a virtual-site description

Sterols play an essential role in modulating bilayer structure and dynamics. Coarse-grained molecular dynamics parameters for cholesterol and related molecules are available for the Martini force field and have been successfully used in multiple lipid bilayer studies. In this work, we focus on the use of virtual sites as a means of increasing the stability of cholesterol and cholesterol-like structures. We improve and extend the Martini parameterization of sterols in four different ways: 1—the cholesterol parameters were adapted to make use of virtual interaction sites, which markedly improves numerical stability; 2—cholesterol parameters were also modified to address reported shortcomings in reproduc- ing correct lipid phase behavior in mixed membranes; 3—parameters for ergosterol were created and adapted from cholesterols; and 4—parameters for the hopanoid class of bacterial polycyclic mole- cules were created, namely, for hopane, diploptene, bacteriohopanetetrol, and for their polycyclic base structure. (C) 2015Author(s).Allarticlecontent,exceptwhereotherwisenoted,islicensedunder a Creative Commons Attribution 3.0 Unported License. [http://dx.doi.org/10.1063/1.4937783

Cross sections for electron impact excitation of the C 1 and D 1+ electronic states in N2O

Differential and integral cross sections for electron-impact excitation of the dipole-allowed C 1Π and D 1Σ+ electronic states of nitrous oxide have been measured. The differential cross sections were determined by analysis of normalized energy-loss spectra obtained using a crossed-beam apparatus at six electron energies in the range 15–200 eV. Integral cross sections were subsequently derived from these data. The present work was undertaken in order to check both the validity of the only other comprehensive experimental study into these excitation processes and to extend the energy range of those data. Agreement with the earlier data, particularly at the lower common energies, was typically found to be fair. In addition, the BEf-scaling approach is used to calculate integral cross sections for the C 1Π and D 1Σ+ states, from their respective thresholds to 5000 eV. In general, good agreement is found between the experimental integral cross sections and those calculated within the BEf-scaling paradigm, the only exception being at the lowest energies of this study. Finally, optical oscillator strengths, also determined as a part of the present investigations, were found to be in fair accordance with previous corresponding determinations

A study of electron scattering from benzene: excitation of the 1B1u, 3E2g, and 1E1u electronic states

We report results from measurements for differential and integral cross sections of the unresolved 1B1u and 3E2g electronic states and the 1E1u electronic state in benzene. The energy range of this work was 10–200 eV, while the angular range of the differential cross sections was -3°–130°. To the best of our knowledge there are no other corresponding theoretical or experimental data against which we can compare the present results. A generalized oscillator strength analysis was applied to our 100 and 200 eV differential cross section data, for both the 1B1u and 1E1u states, with optical oscillator strengths being derived in each case. The respective optical oscillator strengths were found to be consistent with many, but not all, of the earlier theoretical and experimental determinations. Finally, we present theoretical integral cross sections for both the 1B1u and 1E1u electronic states, as calculated within the BEf-scaling formalism, and compare them against relevant results from our measurements. From that comparison, an integral cross section for the optically forbidden 3E2g state is also derived

Synthetic Analogues of the Snail Toxin 6-Bromo-2-mercaptotryptamine Dimer (BrMT) Reveal That Lipid Bilayer Perturbation Does Not Underlie Its Modulation of Voltage-Gated Potassium Channels

Drugs do not act solely by canonical ligand–receptor binding interactions. Amphiphilic drugs partition into membranes, thereby perturbing bulk lipid bilayer properties and possibly altering the function of membrane proteins. Distinguishing membrane perturbation from more direct protein–ligand interactions is an ongoing challenge in chemical biology. Herein, we present one strategy for doing so, using dimeric 6-bromo-2-mercaptotryptamine (BrMT) and synthetic analogues. BrMT is a chemically unstable marine snail toxin that has unique effects on voltage-gated K+ channel proteins, making it an attractive medicinal chemistry lead. BrMT is amphiphilic and perturbs lipid bilayers, raising the question of whether its action against K+ channels is merely a manifestation of membrane perturbation. To determine whether medicinal chemistry approaches to improve BrMT might be viable, we synthesized BrMT and 11 analogues and determined their activities in parallel assays measuring K+ channel activity and lipid bilayer properties. Structure–activity relationships were determined for modulation of the Kv1.4 channel, bilayer partitioning, and bilayer perturbation. Neither membrane partitioning nor bilayer perturbation correlates with K+ channel modulation. We conclude that BrMT’s membrane interactions are not critical for its inhibition of Kv1.4 activation. Further, we found that alkyl or ether linkages can replace the chemically labile disulfide bond in the BrMT pharmacophore, and we identified additional regions of the scaffold that are amenable to chemical modification. Our work demonstrates a strategy for determining if drugs act by specific interactions or bilayer-dependent mechanisms, and chemically stable modulators of Kv1 channels are reported

Substitution effects in elastic electron collisions with CH3X (X = F, Cl, Br, I) molecules

We report absolute elastic differential, integral, and momentum transfer cross sections for electron interactions with the series of molecules CH3X (X = F, Cl, Br, I). The incident electron energy range is 50–200 eV, while the scattered electron angular range for the differential measurements is 15°–150°. In all cases the absolute scale of the differential cross sections was set using the relative flow method with helium as the reference species. Substitution effects on these cross sections, as we progress along the halomethane series CH3F, CH3Cl, CH3Br, and CH3I, are investigated as a part of this study. In addition, atomic-like behavior in these scattering systems is also considered by comparing these halomethane elastic cross sections to results from other workers for the corresponding noble gases Ne, Ar, Kr, and Xe, respectively. Finally we report results for calculations of elastic differential and integral cross sections for electrons scattering from each of the CH3X species, within an optical potential method and assuming a screened corrected independent atom representation. The level of agreement between these calculations and our measurements was found to be quite remarkable in each case

The power of coarse graining in biomolecular simulations

Computational modeling of biological systems is challenging because of the multitude of spatial and temporal scales involved. Replacing atomistic detail with lower resolution, coarse grained (CG), beads has opened the way to simulate large-scale biomolecular processes on time scales inaccessible to all-atom models. We provide an overview of some of the more popular CG models used in biomolecular applications to date, focusing on models that retain chemical specificity. A few state-of-the-art examples of protein folding, membrane protein gating and self-assembly, DNA hybridization, and modeling of carbohydrate fibers are used to illustrate the power and diversity of current CG modeling

A Dynamical (e,2e) Investigation into the Ionization of the Outermost Orbitals of R-Carvone

We report an experimental and theoretical investigation into the dynamics of electron-impact ionization of R-carvone. Experimental triple differential cross sections are obtained in asymmetric coplanar kinematic conditions for the ionization of the unresolved combination of the three outermost molecular orbitals (41a-39a) of R-carvone. These cross sections are compared with theoretical cross sections calculated within a molecular 3-body distorted wave (M3DW) framework employing either a proper orientation average or orbital average to account for the random orientation of the molecule probed in the experiment. Here, we observe that the overall scattering behavior observed in the experiment is fairly well reproduced within the M3DW framework when implementing the proper average over orientations. The character of the ionized orbitals also provides some qualitative explanation for the observed scattering behavior. This represents substantial progress when trying to describe the scattering dynamics observed for larger molecules under intermediate-impact energy and asymmetric energy sharing scattering conditions