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PubMed | Advanced Materials and Processes, Scienomics Sarl, Wroclaw Medical University, National Hellenic Research Foundation and National and Kapodistrian University of Athens
Type: | Journal: Journal of molecular graphics & modelling | Year: 2015

We investigate the binding mechanism in renin complexes, involving three drugs (remikiren, zankiren and enalkiren) and one lead compound, which was selected after screening the ZINC database. For this purpose, we used ab initio methods (the effective fragment potential, the variational perturbation theory, the energy decomposition analysis, the atoms-in-molecules), docking, molecular dynamics, and the MM-PBSA method. A biological assay for the lead compound has been performed to validate the theoretical findings. Importantly, binding free energy calculations for the three drug complexes are within 3 kcal/mol of the experimental values, thus further justifying our computational protocol, which has been validated through previous studies on 11 drug-protein systems. The main elements of the discovered mechanism are: (i) minor changes are induced to renin upon drug binding, (ii) the three drugs form an extensive network of hydrogen bonds with renin, whilst the lead compound presented diminished interactions, (iii) ligand binding in all complexes is driven by favorable van der Waals interactions and the nonpolar contribution to solvation, while the lead compound is associated with diminished van der Waals interactions compared to the drug-bound forms of renin, and (iv) the environment (H2O/Na(+)) has a small effect on the renin-remikiren interaction.

Tsalikis D.G.,National Technical University of Athens | Lempesis N.,National Technical University of Athens | Boulougouris G.C.,National Technical University of Athens | Boulougouris G.C.,University of Western Macedonia | And 3 more authors.
Journal of Physical Chemistry B | Year: 2010

In this work we propose a methodology for improving dynamical sampling in molecular simulations via temperature acceleration. The proposed approach combines the novel methods of Voter for temperature-accelerated dynamics with the multiple histogram reweighting method of Ferrenberg and Swendsen, its dynamical extension by Nieto-Draghi et al., and with hazard plot analysis, allowing optimal sampling with small computational cost over time scales inaccessible to classical molecular dynamics simulations by utilizing the "inherent structure" idea. The time evolution of the system is viewed as a succession of transitions between "basins" in its potential energy landscape, each basin containing a local minimum of the energy (inherent structure). Applying the proposed algorithm to a glass-forming material consisting of a mixture of spherical atoms interacting via Lennard-Jones potentials, we show that it is possible to perform an exhaustive search and evaluate rate constants for basin-to-basin transitions that cover several orders of magnitude on the time scale, far beyond the abilities of any competitive dynamical study, revealing an extreme ruggedness of the potential energy landscape in the vicinity of the glass transition temperature. By analyzing the network of inherent structures, we find that there are characteristic distances and rate constants related to the dynamical entrapment of the system in a neighborhood of basins (a metabasin), whereas evidence to support a random energy model is provided. The multidimensional configurational space displays a self-similar character depicted by a fractal dimension around 2.7 (±0.5) for the set of sampled inherent structures. Only transitions with small Euclidean measure can be considered as localized. © 2010 American Chemical Society.

Tsalikis D.G.,National Technical University of Athens | Lempesis N.,National Technical University of Athens | Boulougouris G.C.,National Technical University of Athens | Boulougouris G.C.,University of Western Macedonia | And 3 more authors.
Journal of Chemical Theory and Computation | Year: 2010

In this work, we propose a highly parallelizable sampling scheme designed for atomistic simulations of glassy materials in the vicinity of the glass-transition temperature Tg, based on the idea of inherent structures (IS). Glassy dynamics is envisioned as a combination of two types of motions: (a) an "in basin" vibrational motion in the vicinity of a potential energy minimum (IS), and (b) transitions from one basin to another. In order to perform efficient dynamical sampling in the vicinity of Tg, we propose an "on the fly" definition of metabasins (i.e., collections of basins communicating via fast transitions in which the system spends a sufficient time before moving on to a neighboring collection). Our criterion for defining metabasins is based on the rate of identification of new basins in the course of a canonical molecular dynamics (MD) run. In order to compute individual rate constants between basins and metabasins, we propose to follow a swarm of microcanonical MD trajectories initiated at phase-space points sampled by a canonical MD run that is artificially trapped within a metabasin. The execution time required by this highly parallelizable scheme is reduced dramatically, since no information exchange takes place between the microcanonical trajectories. Results from our parallel methodology are compared against results from artificially trapped canonical MD runs, in terms of the evaluated rate constants, and found to be in very good agreement. Parallel simulations have been conducted on up to 250 processors, achieving almost linear scaling. The validity of our definition of metabasins is confirmed by analysis of the resulting network of basins. © 2010 American Chemical Society.

Boulougouris G.C.,University of Patras | Boulougouris G.C.,Scienomics SARL
Journal of Chemical and Engineering Data | Year: 2010

The estimation of the chemical potential is crucial in a variety of applications involving phase equilibrium. The heart of such calculation lies in the evaluation of a free-energy difference usually in the form of a partition function ratio. In this work, a general formulation is proposed for the calculation of the chemical potential from molecular simulation based on an integrated form of the first-order free-energy perturbation theory, which is able to overcome the main obstacle of the traditional first-order free-energy perturbation theory. The formulation is based on a novel scheme, where the perturbation is performed in an integral over a set of degrees of freedom. Beyond the general formalism, a specific example is presented leading to a reinsertion scheme for the evaluation of the chemical potential. Calculations based on this scheme are in excellent agreement with predictions from an accurate equation of state and equivalent to the test particle insertion scheme (Widom insertion scheme) for the pure Lennard-Jones fluid at high densities from NVT Monte Carlo simulations. The proposed method has a straightforward implementation and can be combined with the traditional test particle insertion method (Widom, B. J. Chem. Phys. 1982, 86, 869.). Furthermore, since test particle insertion estimates the excess chemical potential as a forward difference and the proposed reinsertion scheme as a backward difference, their combination can be used as a consistency check to ensure efficient sampling. © 2010 American Chemical Society.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENERGY.2011.5.1-1 | Award Amount: 5.77M | Year: 2011

The current requirements of the Post Combustion CO2 Capture (PCC) technology are: a) Reducing the parasitic energy load, b) Effectively addressing corrosion, c) Faster absorption/stripping rates, d) Less viscosity and less use of water, e) Confronting the problem of solvent degradation and volatility. These problems pose stimulating challenges for the synthesis of new solvents, aided by detailed molecular modeling of sorbate/sorbent interactions, and for new integrative module designs that enable their effective implementation in a process environment. In this context the IOLICAP proposal gathers expertise and skills form the domains of chemical synthesis of Ionic Liquids (ILs), molecular simulation/mechanical statistics, phase equilibrium, electrochemistry/corrosion, physicochemical/thermophysical characterisation, nanoporous materials & membrane technology and process engineering, aiming at the development and evaluation of novel Task Specific Ionic Liquid (TSILs) solvents that (a) short-term could replace the alkanolamines in currently existing PCC installations and (b) long-term would lead to the establishment of a novel CO2 capture process, based on hybrid absorption bed/membrane technology that will incorporate TSIL modified porous materials and membranes. Task Specific Ionic Liquids exhibit enhanced CO2 capture capacity, which is above the 0.5 mol/mol limit of the currently applied amine solvents. Due to the high number of possible IL structures that will be synthesised during the project and the easy tuneability of their chemical and physical properties it is expected that loading capacities above the threshold of 1 mol/mol will be achieved. In addition, ILs are less corrosive than amines and are dissociated so there is no need for using large quantities of water. ILs are also less volatile and less sensitive to flue gas impurities a fact that ensures less need for timely injection of fresh solvent. The aforementioned properties which will be studied and verified during the project, will have a high impact on the energy intensity of the capture process since they can lead to a significant reduction of the Scrubber/Stripper units size and consequently of the parasitic energy load. Ionic Liquid membranes are lately examined as candidates for CO2/N2 separation exhibiting performances that are above the boundary limit of a Roberson plot for this separation. IOLICAP project targets at the optimisation of the stability, selectivity (200), flux properties (1000-2000 Barrers) and production cost of Task Specific Ionic Liquid membranes and at the further enhancement of the process efficiency, through a combination of membrane technology with bed adsorption. Membrane technology is the less energy intensive candidate for CO2/N2 separation since there is no need for regeneration and constitutes a much more versatile and economically feasible technology especially for applications in energy intensive industry like the cement, steel and refineries.

Salpage S.R.,University of South Carolina | Donevant L.S.,University of South Carolina | Smith M.D.,University of South Carolina | Bick A.,Scienomics SARL | Shimizu L.S.,University of South Carolina
Journal of Photochemistry and Photobiology A: Chemistry | Year: 2016

This manuscript reports on the modulation of the photoreactivity of a series of chromones, also known as benzo-γ-pyrones, by absorption into a porous self-assembled host formed from phenylethynylene bis-urea macrocycles. Chromone and four derivatives namely 6-fluorochromone, 6-bromochromone, 7-hydroxy-4-chromone, and 3-cyanochromone are unreactive in the solid-state. Each of these derivatives was loaded into the nanochannels of self-assembled phenylethynylene bis-urea macrocycles to form solid host·guest complexes, which were subsequently UV-irradiated at room temperature under argon atmosphere. We observed that chromone and 6-fluorochromone underwent selective [2 + 2] photodimerization reactions to produce anti-HT dimers in high selectivity and conversion. The 6-bromochromone also reacted in high selectivity and conversion to afford an aryl coupling adduct. In each case, the products were extracted, and the crystalline host recovered. In comparison, 7-hydroxy-4-chromone, and 3-cyanochromone were unreactive within the complex. Simple GCMC simulation studies suggest that chromone, 6-fluorochromone, and 6-bromochromone were loaded in orientations that facilitate photoreaction, and correctly predicted that the anti-HT dimer would be favored in the chromone case. In contrast, syn-HH dimers were predicted by GCMC simulations for the halogen containing derivatives but were not observed. The simulations with 7-hydroxy-4-chromone were in agreement with the observed reactivity. We compare these computational and experimental findings and suggest future methods for optimizing simulation parameters. Our goal is to expand the scope and accuracy of the simulations to be able to predict the reactivity of guests encapsulated within columnar nanotubes. © 2015 Elsevier B.V.

Lithoxoos G.P.,Greek National Center For Scientific Research | Lithoxoos G.P.,Scienomics Sarl | Peristeras L.D.,Scienomics Sarl | Boulougouris G.C.,Greek National Center For Scientific Research | And 2 more authors.
Molecular Physics | Year: 2012

In this study, the adsorption capacity of pure and activated carbon with regard to carbon monoxide (CO), carbon dioxide (CO 2) and methane (CH 4) gases at 298K and pressure from 0.01 up to 2.0MPa has been investigated computationally. Computational work refers to Monte Carlo (MC) simulation of each adsorbed gas on a graphite model with varying density of activation sites. The Grand Canonical Monte Carlo (GCMC) simulation technique was employed to obtain the uptake of each adsorbed gas by considering a graphite model of parallel sheets activated by carboxyl and hydroxyl groups, as observed experimentally. The simulation adsorption data for these gases within the examined carbon pore material are presented and discussed in terms of the adsorbate fluid molecular characteristics and corresponding interactions between adsorbate species and adsorbent material. We found that the simulated adsorption uptake of the examined graphite model under these conditions with regard to the aforementioned fluids increases in the order CO

Boulougouris G.C.,Democritius University | Boulougouris G.C.,Scienomics SARL
Journal of Physical Chemistry B | Year: 2012

In this work, we propose the evaluation of the free energy in molecular systems, in a "single" step, by "deleting" all the molecules in the system. The approach can be considered as the statistical mechanics analogue of the evaluation of the potential energy in classical mechanics by accounting for the necessary work to transfer all particles one by one to infinite distance. As a result, the free energy of an atomistic system can now be expressed as an ensemble average over a configurational function that corresponds to the contribution of each microstate to the free energy of the ensemble. Moreover, the proposed method is capable of evaluating the free energy as a function of the density, from the simulated density down to zero. Finally, the proposed method is related to the Rosenbluth sampling of the inverse process, that of inserting (instead of deleting) and provide the analogous theorems to Bennett's and Crooks' work (Bennett, C. H.J. Comput. Phys. 1976, 22, 245; Crooks, G. E.Phys. Rev. E 1999, 60, 2721). When the proposed process is envisioned as the transformation of an interacting to a noninteracting system, the proposed scheme reduces to the Jarzynski identity linking the free energy of the system to the chemical work related to this transformation. © 2011 American Chemical Society.

Boulougouris G.C.,Democritius University | Boulougouris G.C.,Scienomics SARL | Boulougouris G.C.,Advanced Materials and Processes
Journal of Chemical Physics | Year: 2013

In this work we propose a multidimensional free energy perturbation scheme that allows the evaluation of the free energy difference between a state sampled based on importance sampling and almost any state that can be constructed by the reduction of the number of molecules in the system and the change of either the interaction energy or the thermodynamic state variable (e.g., the temperature) of the system. We show that via this approach it is possible to evaluate any thermodynamic property included but not limited to free energy, chemical potential, and pressure, along a series of isotherms from a single molecular simulation. © 2013 American Institute of Physics.

Takis P.G.,University of Ioannina | Papavasileiou K.D.,University of Ioannina | Peristeras L.D.,Scienomics Sarl | Melissas V.S.,University of Ioannina | Troganis A.N.,University of Ioannina
Physical Chemistry Chemical Physics | Year: 2013

How many solvent molecules and in what way do they interact directly with biomolecules? This is one of the most challenging questions regarding a deep understanding of biomolecular functionalism and solvation. We herein present a novel NMR spectroscopic study, achieving for the first time the quantification of the directly interacting water molecules with several neutral dipeptides. Our proposed method is supported by both molecular dynamics simulations and density functional theory calculations, advanced analysis of which allowed the identification of the direct interactions between solute-solvent molecules in the zwitterionic l-alanyl-l-alanine dipeptide-water system. Beyond the quantification of dipeptide-water molecule direct interactions, this NMR technique could be useful for the determination and elucidation of small to moderate bio-organic molecular groups' direct interactions with various polar solvent molecules, shedding light on the biomolecular micro-solvation processes and behaviour in various solvents. © 2013 the Owner Societies.

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