Structural Phenomena in a Vesicle Membrane Obtained through an Evolution Experiment: A Study Based on MD Simulations.

The chemical evolution of biomolecules was clearly affected by the overall extreme environmental conditions found on Early Earth. Periodic temperature changes inside the Earth's crust may have played a role in the emergence and survival of functional peptides embedded in vesicular compartments. In this study, all-atom molecular dynamic (MD) simulations were used to elucidate the effect of temperature on the properties of functionalized vesicle membranes. A plausible prebiotic system was selected, constituted by a model membrane bilayer from an equimolar mixture of long-chain fatty acids and fatty amines, and an octapeptide, KSPFPFAA, previously identified as an optimized functional peptide in an evolution experiment. This peptide tends to form the largest spontaneous aggregates at higher temperatures, thereby enhancing the pore-formation process and the eventual transfer of essential molecules in a prebiotic scenario. The analyses also suggest that peptide-amphiphile interactions affect the structural properties of the membrane, with a significant increase in the degree of interdigitation at the lowest temperatures under study.

Membrane Structure Obtained in an Experimental Evolution Process.

Recently, an evolution experiment was carried out in a cyclic process, which involved periodic vesicle formation in combination with peptide and vesicle selection. As an outcome, an octapeptide (KSPFPFAA) was identified which rapidly integrated into the vesicle membrane and, according to its significant accumulation, is obviously connected to a particular advantage of the corresponding functionalized vesicle. Here we report a molecular dynamics study of the structural details of the functionalized vesicle membrane, which was a product of this evolution process and is connected to several survival mechanisms. In order to elucidate the particular advantage of this structure, we performed all-atom molecular dynamics simulations to examine structural changes and interactions of the peptide (KSPFPFAA) with the given octadecanoic acid/octadecylamine (1:1) bilayer under acidic conditions. The calculations clearly demonstrate the specific interactions between the peptide and the membrane and reveal the mechanisms leading to the improved vesicle survival.

Molecular Evolution in a Peptide-Vesicle System.

Based on a new model of a possible origin of life, we propose an efficient and stable system undergoing structural reproduction, self-optimization, and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offers vesicles as the structural environment, with the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution, and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time would not only represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence for a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to (i) reduced vesicle size, (ii) increased vesicle membrane permeability, and (iii) improved thermal vesicle stability.

Selection of Prebiotic Molecules in Amphiphilic Environments.

A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds, like nucleobases, sugars or peptides, principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments.

Periodic Vesicle Formation in Tectonic Fault Zones--an Ideal Scenario for Molecular Evolution.

Tectonic fault systems in the continental crust offer huge networks of interconnected channels and cavities. Filled mainly with water and carbon dioxide (CO2), containing a wide variety of hydrothermal chemistry and numerous catalytic surfaces, they may offer ideal reaction conditions for prebiotic chemistry. In these systems, an accumulation zone for organic compounds will develop at a depth of approximately 1 km where CO2 turns sub-critical and dissolved components precipitate. At this point, periodic pressure changes caused for example by tidal influences or geyser activity may generate a cyclic process involving repeated phase transitions of carbon dioxide. In the presence of amphiphilic compounds, this will necessarily lead to the transient formation of coated water droplets in the gas phase and corresponding vesicular structures in the aqueous environment. During this process, the concentration of organic components inside the droplets and vesicles would be drastically increased, allowing for favorable reaction conditions and, in case of the vesicles generated, large trans-membrane concentration gradients. Altogether, the process of periodic formation and destruction of vesicles could offer a perfect environment for molecular evolution in small compartments and for the generation of protocells. The basic process of vesicle formation is reproduced experimentally with a lipid in a water/CO2 system.

Disability transitions after 30 months in three community-dwelling diagnostic groups in Spain.

BACKGROUND: Little is known about changes in disability over time among community-dwelling patients. Accordingly, this study sought to assess medium-term disability transitions. PATIENTS AND METHODS: 300 chronic obstructive pulmonary disease (COPD), chronic heart failure and stroke patients living at home in Madrid were selected from general practitioner lists. In 2009, disability was assessed after a mean of 30 months using the World Health Organisation (WHO) Disability Assessment Schedule 2.0 (WHODAS 2.0). Follow-up was completed using death registries. Losses to follow-up were due to: death, 56; institutionalisation, 9; non-location, 18; and non-participation, 17. Changes in WHODAS 2.0 scores and life status were described and analysed using Cox and multinomial regression. Disability at end of follow-up was imputed for 56 deceased and 44 surviving patients. RESULTS: Mean disability scores for 200 surviving patients at end of follow-up were similar to baseline scores for the whole group, higher than their own baseline scores, and rose by 16.3% when imputed values were added. The strongest Cox predictors of death were: age over 84 years, adjusted hazard ratios with 95%CI 8.18 (3.06-21.85); severe/complete vs. no/mild disability, 5.18 (0.68-39.48); and stroke compared to COPD, 1.40 (0.67-2.91). Non-participants and institutionalised patients had higher proportions with severe/complete baseline disability. A one-point change in baseline WHODAS 2.0 score predicted independent increases in risk of 12% (8%-15%) for severe/complete disability or death. CONCLUSIONS: A considerably high proportion of community-dwelling patients diagnosed with COPD, CHF and stroke undergo medium-term changes in disability or vital status. The main features of the emerging pattern for this group appear to be as follows: approximately two-thirds of patients continue living at home with moderately reduced functional status; 1/3 die or worsen to severe/complete disability; and 1/10 improve. Baseline disability scores, age and diagnosis are associated with disability and death in the medium term.

Measurements and predictive models for the N-methyl-2-pyrrolidone/water/methanol system.

This work reports on the properties and structure of N-methyl-2-pyrrolidone in binary and ternary liquid mixtures with water and/or methanol. A comprehensive set of thermophysical properties have been measured at 298.15 K and 0.1 MPa over the whole composition range. On the basis of the derived excess and mixing properties, the fluid structure was analyzed by looking into the forces and geometry factors that effectively control the mixture behavior. Application of the inverted Kirkwood-Buff theory provides a reasonable link between the macroscopic properties and the microscopic features. A density functional theory computation was carried out to analyze the structure and energy features of the hydrogen bonded complexes formed between the components. Use of semiempirical models in the framework of molecular-based equations of state according to the PC-SAFT approach led to unsatisfactory predicted thermophysical properties. The conclusions arrived at give away the existence of strong heteroassociations and hydrogen bonding self-associations that determine the complex nature of the fluid structure.

On the properties of methylbenzoate/n-hexane mixed solvents: a theoretical and experimental study.

This paper reports on an experimental and theoretical study of methylbenzoate/n-hexane mixed solvents as a function of pressure and temperature in the whole composition range. We have measured the pressure-volume-temperature (PVT) behavior of these fluids over wide temperature and pressure ranges; from the experimental data, relevant derived coefficients required for the fluid's characterization were calculated. The structure of mixed fluids was analyzed from macroscopic data according to excess and mixing properties. The statistical associating fluid theory (SAFT) and perturbed chain (PC)-SAFT molecularly based equations of state were used to predict the PVT behavior with model parameters for pure fluids fitted from correlation of available saturation literature data. The results provided by the PC-SAFT equation of state were clearly superior. Using the fitted PC-SAFT parameters, the global phase behavior of the mixture was predicted, and a type I pattern was inferred according to the van Konynenburg systematic. The molecular level structure was studied through classical molecular dynamics simulations in the NPT ensemble using the optimized potential for liquid simulations (all atom version) (OPLS-AA) force field. Molecular dynamics provides, on one hand, theoretical values of thermophysical properties, which are compared with the experimental ones to check the quality of simulations, and, on the other hand, valuable molecular level structural and dynamic information. Based on both macroscopic and microscopic studies, fluid structure was inferred.

Properties and structure of aromatic ester solvents.

This paper reports on an experimental and theoretical study of the aromatic ester solvents family. Several compounds were selected to analyze the different factors that influence their liquid-state properties and structures. The pressure-volume-temperature behavior of these fluids was measured accurately over wide temperature and pressure ranges and correlated successfully with the empirical TRIDEN equation. From the measured data the relevant derived coefficients of isothermal compressibility, isobaric expansibility, and internal pressure were calculated. The statistical associating fluid theory (SAFT) and perturbed chain statistical associating fluid theory (PC-SAFT) molecularly based equations of state were used to predict the PVT behavior with model parameters obtained from the correlation of available saturation literature data; the results provided by PC-SAFT equations of state were clearly superior for all of the studied solvents. The fluid's molecular level structure was studied by quantum computations at the B3LYP/6-311++g** level and classical molecular dynamics simulations in the NPT ensemble with the OPLS-AA forcefield. Molecular parameters, such as torsional barriers or cluster energetics, were analyzed as a function of ester structures. The molecular dynamics study provides, on one hand, theoretical values of thermophysical properties, which are compared with the experimental ones, and, on the other hand, valuable molecular level structural information. On the basis of both macroscopic and microscopic studies complex fluid structures were inferred with important effects arising from the geometries of the studied molecules and from the existence of remarkable intermolecular forces of dominating dipolar nature.

Properties of 1,8-cineole: a thermophysical and theoretical study.

This paper reports on an experimental and theoretical study of 1,8-cineole, one of the main components of essential oils in different plants. The pressure-volume-temperature behavior of this fluid was evaluated accurately over wide temperature and pressure ranges and correlated successfully with the empirical TRIDEN equation. From the measured data, the relevant derived coefficients isothermal compressibility, isobaric expansibility, and internal pressure were calculated. The isobaric heat capacities at high pressure were extrapolated from the data measured at atmospheric pressure. The cubic equations of state by Soave, Peng-Robinson, Stryjek-Vera modification of Peng-Robinson, Patel-Teja, Sako-Wu-Prausnitz, and the SAFT and PC-SAFT molecularly based equations of state were used to predict the PVT behavior. The SAFT and PC-SAFT parameters for 1,8-cineole were obtained from correlation of available saturation literature data; the best results were provided by Sako-Wu-Prausnitz and PC-SAFT equations of state, whereas the classical ones were shown to be inadequate. The molecular structure was studied by quantum computations at the B3LYP/6-311++g(d) level and classical molecular dynamics simulations in the NPT ensemble with the OPLS-AA forcefield. On the basis of both macroscopic and microscopic studies, a complex fluid structure was inferred.

PVTx measurements of the N-methylpyrrolidone/methanol mixed solvent: cubic and SAFT EOS analyses.

The PVTx behavior for the x N-methylpyrrolidone (NMP) + (1 - x) methanol compressed liquid solvent is reported over the full composition range and within wide pressure and temperature ranges. The derived excess properties were analyzed in terms of structural effects and intermolecular interactions and revealed strong H-bonding heteroassociations between the two components. The cubic equations of state by Soave (SRK), Peng-Robinson (PR), Patel-Teja (PT), and Sako-Wu-Prausnitz (SWP), and the statistical associating fluid theory (SAFT) equation of state, combined with a number of selected mixing rules, were used to correlate and predict the behavior of both the pure components and mixed solvent. While the classical cubic equations of state were not successful in describing the properties of this system, the SWP equation of state and the SAFT yielded reasonably good results.