Direct comparison of elastic incoherent neutron scattering experiments with molecular dynamics simulations of DMPC phase transitions.

Neutron scattering techniques have been employed to investigate 1,2-dimyristoyl-sn -glycero-3-phosphocholine (DMPC) membranes in the form of multilamellar vesicles (MLVs) and deposited, stacked multilamellar-bilayers (MLBs), covering transitions from the gel to the liquid phase. Neutron diffraction was used to characterise the samples in terms of transition temperatures, whereas elastic incoherent neutron scattering (EINS) demonstrates that the dynamics on the sub-macromolecular length-scale and pico- to nano-second time-scale are correlated with the structural transitions through a discontinuity in the observed elastic intensities and the derived mean square displacements. Molecular dynamics simulations have been performed in parallel focussing on the length-, time- and temperature-scales of the neutron experiments.

Perspectives in biological physics: the nDDB project for a neutron Dynamics Data Bank for biological macromolecules.

Neutron spectroscopy provides experimental data on time-dependent trajectories, which can be directly compared to molecular dynamics simulations. Its importance in helping us to understand biological macromolecules at a molecular level is demonstrated by the results of a literature survey over the last two to three decades. Around 300 articles in refereed journals relate to neutron scattering studies of biological macromolecular dynamics, and the results of the survey are presented here.

Evidence of dynamical constraints imposed by water organization around a bio-hydrophobic interface.

Molecular dynamics simulations and elastic neutron scattering experiments have been used to highlight how the structural organization of hydration water is able in some cases to locally constrain atomic movements at biologic interfaces. Using fully hydrated small peptides as models of protein interfaces, we show that the length of the side chains and the hydrophilic backbone have specific signatures. The dynamics of the side chain, which is part of biomolecules, have not only a crucial role in the whole flexibility as compared to the backbone, but also modify the values of transition temperatures.

nMoldyn 3: using task farming for a parallel spectroscopy-oriented analysis of molecular dynamics simulations.

We present a new version of the program package nMoldyn, which has been originally developed for a neutron-scattering oriented analysis of molecular dynamics simulations of macromolecular systems (Kneller et al., Comput. Phys.

Dynamics-stability relationships in apo- and holomyoglobin: a combined neutron scattering and molecular dynamics simulations study.

The removal of the heme group from myoglobin (Mb) results in a destabilization of the protein structure. The dynamic basis of the destabilization was followed by comparative measurements on holo- (holo-Mb) and apomyoglobin (apo-Mb). Mean-squared displacements (MSD) and protein resilience on the picosecond-to-nanosecond timescale were measured by elastic incoherent neutron scattering.

Vibrational density of states of hydration water at biomolecular sites: hydrophobicity promotes low density amorphous ice behavior.

Inelastic neutron scattering experiments and molecular dynamics simulations have been used to investigate the low frequency modes, in the region between 0 and 100 meV, of hydration water in selected hydrophilic and hydrophobic biomolecules. The results show changes in the plasticity of the hydrogen-bond network of hydration water molecules depending on the biomolecular site. At 200 K, the measured low frequency density of states of hydration water molecules of hydrophilic peptides is remarkably similar to that of high density amorphous ice, whereas, for hydrophobic biomolecules, it is comparable to that of low density amorphous ice behavior.

In vivo molecular imaging of myocardial angiogenesis using the alpha(v)beta3 integrin-targeted tracer 99mTc-RAFT-RGD.

Background: Myocardial angiogenesis following reperfusion of an infarcted area may impact on patient prognosis and pro-angiogenic treatments are currently evaluated. The non-invasive imaging of angiogenesis would therefore be of potential clinical relevance in these settings. (99m)Tc-RAFT-RGD is a novel (99m)Tc-labeled tracer that targets the alpha(v)beta(3) integrin.

Use of structure descriptors to discriminate between modes of toxic action of phenols.

Two classification models were developed based on a data set of 220 phenols with four associated Modes of Toxic Action (MOA). Counter-propagation neural networks (CPG NN) and multinomial logistic regression (multinom) were used as classification methods. The combination of topological autocorrelation of empirical pi-charge and sigma-electronegativity and of surface autocorrelation of hydrogen-bonding potential resulted in a 21-dimensional model that successfully discriminated between the four MOAs.

Development and testing of a de novo drug-design algorithm.

In this article we present an implementation of a de novo drug-design algorithm. The algorithm starts with a molecule placed in the binding site of a protein and then modifies it using a sequential growth approach. This involves successive cycles of suppression of randomly picked groups in the molecule and their replacement by other groups chosen from databanks of linear or cyclic fragments.

Transition events in one dimension.

The instanton or stationary-phase formula has received much attention recently as a way of determining transition paths in reacting systems. In this paper, we analyze the instanton approach for some one-dimensional problems and compare the results it gives with data from a numerical simulation. We show that a proper comparison of the analytic and numerical results must take into account the boundary conditions used in the numerical simulations and also suggest values for the integration constant in the instanton formula that gives the best agreement with the simulated results.