Structures Controlled by Entropy: The Flexibility of Strychnine as Example

To study the flexibility of strychnine, we performed molecular dynamics simulations with orientational tensorial constraints (MDOC). Tensorial constraints are derived from nuclear magnetic resonance (NMR) interaction tensors, for instance, from residual dipolar couplings (RDCs). Used as orientational constraints, they rotate the whole molecule and molecular parts with low rotational barriers. Since the NMR parameters are measured at ambient temperatures, orientational constraints generate conformers that populate the whole landscape of Gibbs free energy. In MDOC, structures are populated that are not only controlled by energy but by the entropy term TΔS of the Gibbs free energy. In the case of strychnine, it is shown that ring conformers are populated, which has not been discussed in former investigations. These conformer populations are not only in accordance with RDCs but fulfill nuclear Overhauser effect (NOE)-derived distance constraints and $^{3}J_{HH}$ couplings as well

All-atom molecular dynamics simulations using orientational constraints from anisotropic NMR samples

Orientational constraints obtained from solid state NMR experiments on anisotropic samples are used here in molecular dynamics (MD) simulations for determining the structure and dynamics of several different membrane-bound molecules. The new MD technique is based on the inclusion of orientation dependent pseudo-forces in the COSMOS-NMR force field. These forces drive molecular rotations and re-orientations in the simulation, such that the motional time-averages of the tensorial NMR properties approach the experimentally measured parameters. The orientational-constraint-driven MD simulations are universally applicable to all NMR interaction tensors, such as chemical shifts, dipolar couplings and quadrupolar interactions. The strategy does not depend on the initial choice of coordinates, and is in principle suitable for any flexible molecule. To test the method on three systems of increasing complexity, we used as constraints some deuterium quadrupolar couplings from the literature on pyrene, cholesterol and an antimicrobial peptide embedded in oriented lipid bilayers. The MD simulations were able to reproduce the NMR parameters within experimental error. The alignment of the three membrane-bound molecules and some aspects of their conformation were thus derived from the NMR data, in good agreement with previous analyses. Furthermore, the new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of all three systems

Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT). Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges of ab initio calculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation of R=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angle χ1 and small variations of χ2 of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism

Properties of a Variable-delay Polarization Modulator

We investigate the polarization modulation properties of a variable-delay polarization modulator (VPM). The VPM modulates polarization via a variable separation between a polarizing grid and a parallel mirror. We find that in the limit where the wavelength is much larger than the diameter of the metal wires that comprise the grid, the phase delay derived from the geometric separation between the mirror and the grid is sufficient to characterize the device. However, outside of this range, additional parameters describing the polarizing grid geometry must be included to fully characterize the modulator response. In this paper, we report test results of a VPM at wavelengths of 350 microns and 3 mm. Electromagnetic simulations of wire grid polarizers were performed and are summarized using a simple circuit model that incorporates the loss and polarization properties of the device.Comment: 25 pages, 10 figures, accepted by Applied Optic

Configuration determination by residual dipolar couplings: accessing the full conformational space by molecular dynamics with tensorial constraints

Residual dipolar couplings (RDCs) and other residual anisotropic NMR parameters provide valuable structural information of high quality and quantity, bringing detailed structural models of flexible molecules in solution in reach. The corresponding data interpretation so far is directly or indirectly based on the concept of a molecular alignment tensor, which, however, is ill-defined for flexible molecules. The concept is typically applied to a single or a small set of lowest energy structures, ignoring the effect of vibrational averaging. Here, we introduce an entirely different approach based on time averaged molecular dynamics with dipolar couplings as tensorial orientational restraints that can be used to solve structural problems in molecules of any size without the need of introducing an explicit molecular alignment tensor into the computation. RDC restraints are represented by their full 3D interaction tensor in the laboratory frame, for which pseudo forces are calculated using a secular dipolar Hamiltonian as the target. The resulting rotational averaging of each individual tensorial restraint leads to structural ensembles that best fulfil the experimental data. Using one-bond RDCs, the approach has been implemented in the force field procedures of the program COSMOS and extensively tested. A concise theoretical introduction, including the special treatment of force fields for stable and fast MD simulations, as well as applications regarding configurational analyses of small to medium-sized organic molecules with different degrees of flexibility, is given. The observed results are discussed in detail

Shifts of criteria or neural timing? The assumptions underlying timing perception studies

In timing perception studies, the timing of one event is usually manipulated relative to another, and participants are asked to judge if the two events were synchronous, or to judge which of the two events occurred first. Responses are analyzed to determine a measure of central tendency, which is taken as an estimate of the timing at which the two events are perceptually synchronous. When these estimates do not coincide with physical synchrony, it is often assumed that the sensory signals are asynchronous, as though the transfer of information concerning one input has been accelerated or decelerated relative to the other. Here we show that, while this is a viable interpretation, it is equally plausible that such effects are driven by shifts in the criteria used to differentiate simultaneous from asynchronous inputs. Our analyses expose important ambiguities concerning the interpretation of simultaneity judgement data, which have hitherto been underappreciated

Facilitating creative thinking in the classroom: investigating the effects of plants and the colour green on visual and verbal creativity

We report upon a study concerned with the effect of exposure to live plants, views to nature and the colour green upon visual and verbal creativity. The study reported in this paper was undertaken with 108 business students at a British University who were randomly allocated to one of the three conditions. The control group were placed in a classroom with no plants present and blinds drawn to block view to natural settings, the first experimental group were placed in a classroom with no plants present, blinds drawn to block views to nature but completed the creativity tasks on green paper. The second experimental group were placed in the same room as the other groups, but were surrounded by live plants and had views to nature through the large classroom windows. All participants completed two creativity tasks; a visual creativity task and a verbal creativity task. Visual creativity was assessed using a modified version of Amabile's Consensual Assessment Technique (Amabile, 1982). Verbal creative was assessed using a modified scoring method of Guilford's alternative uses task developed by Silvia (2008). Findings indicate that access to natural views, plants and the colour green increase visual creativity, but have no impact on verbal creativity in classroom settings. The results suggest that creativity is domain specific and any practical measures taken to enhance creativity need to be aligned with the target domain

The Reality of Wellbeing-Focused Design in Dementia Care – A Case Study of Acute Dementia Wards in the UK

Objective. The study explored design for wellbeing within dementia-care by investigating the adoption of wellbeing-focused design in real-world practice, through observing NHS wards. Background. Design for wellbeing is an approach that considers the psychological and physiological effects of architecture to improve health and wellbeing. The high psychological care requirement for dementia patients makes them a significant group to study in the evaluation of current hospital facilities. Methods. A literature review was conducted, to frame the current theoretical perception of the key characteristics of a good environment for dementia care. A framework was generated to summarise, and used as an assessment tool in a series of observational visits to NHS wards. Interviews with clinical staff focused on care outcomes and practicalities of implementing wellbeing-focused design, considering the historical and economical context. Key findings from the observations and interviews were analysed for recurring themes. Results. The ward observations and interviews provided insight to the current progression of wellbeing-led design in NHS hospitals in England. The research highlights key areas of success, and factors that inhibit further progression. Conclusions. The case studies showed a good degree of ambition to utilise wellbeing-focused design, with belief among staff that the physical environment has a substantial role in the health and wellbeing of patients. Staff also felt that this approach is most effective for those in the less advanced stages of dementia. Despite the high level of support, the current degree of implementation appears to be varied

Temporal processes in prime–mask interaction: Assessing perceptual consequences of masked information

Visual backward masking is frequently used to study the temporal dynamics of visual perception. These dynamics may include the temporal features of conscious percepts, as suggested, for instance, by the asynchronous–updating model (Neumann, 1982) and perceptual–retouch theory ((Bachmann, 1994). These models predict that the perceptual latency of a visual backward mask is shorter than that of a like reference stimulus that was not preceded by a masked stimulus. The prediction has been confirmed by studies using temporal–order judgments: For certain asynchronies between mask and reference stimulus, temporal–order reversals are quite frequent (e.g. Scharlau, & Neumann, 2003a). However, it may be argued that these reversals were due to a response bias in favour of the mask rather than true temporal-perceptual effects. I introduce two measures for assessing latency effects that (1) are not prone to such a response bias, (2) allow to quantify the latency gain, and (3) extend the perceptual evidence from order reversals to duration/interval perception, that is, demonstrate that the perceived interval between a mask and a reference stimulus may be shortened as well as prolonged by the presence of a masked stimulus. Consequences for theories of visual masking such as asynchronous–updating, perceptual–retouch, and reentrant models are discussed