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Hannes Jónsson - One of the best experts on this subject based on the ideXlab platform.

  • Reversible Work transition state theory: application to dissociative adsorption of hydrogen
    Surface Science, 1995
    Co-Authors: Gregory Mills, Hannes Jónsson, Gregory K. Schenter
    Abstract:

    Abstract A practical method for finding free energy barriers for transitions in high-dimensional classical and quantum systems is presented and used to calculate the dissociative sticking probability of H 2 on a metal surface within the transition state theory. The Reversible Work involved in shifting the system confined to a hyperplane from the reactant region towards products is evaluated directly. Quantum mechanical degrees of freedom are included by using Feynman path integrals with the hyperplane constraint applied to the centroid of the cyclic paths. An optimal dividing surface for the rate estimated by the transition state theory is identified naturally in the course of the Reversible Work evaluation. The free energy barrier is determined relative to the reactant state directly so that an estimate of the transition rate can be obtained without requiring a solvable reference model for the transition state. The method has been applied to calculations of the sticking probability of a thermalized hydrogen gas on a Cu(110) surface. The two hydrogen atoms and eight surface Cu atoms were included quantum mechanically and over two hundred atoms in the Cu crystal where included classically. The activation energy for adsorption and desorption was determined and found to be significantly lowered by tunneling at low temperature. The calculated values agree quite well with experimental estimates for adsorption and desorption. Dynamical corrections to the classical transition state theory rate estimate were evaluated and found to be small.

  • Reversible Work transiton state theory application to dissociative adsorption of hydrogen
    arXiv: Chemical Physics, 1994
    Co-Authors: Gregory Mills, Hannes Jónsson
    Abstract:

    A practical method for finding free energy barriers for transitions in high-dimensional classical and quantum systems is presented and used to calculate the dissociative sticking probability of H2 on a metal surface within transition state theory (TST). The Reversible Work involved in shifting the system confined to a hyperplane from the reactant region towards products is evaluated directly. Quantum mechanical degrees of freedom are included by using Feynman Path Integrals with the hyperplane constraint applied to the centroid of the cyclic paths. An optimal dividing surface for the rate estimated by TST is identified naturally in the course of the Reversible Work evaluation. The free energy barrier is determined relative to the reactant state directly, so an estimate of the transition rate can be obtained without requiring a solvable reference model for the transition state. The method has been applied to calculations of the sticking probability of a thermalized hydrogen gas on a Cu(110) surface. The two hydrogen atoms were included quantum mechanically, and over two hundred atoms in the Cu crystal where included classically. The activation energy for adsorption and desorption was determined and found to be significantly lowered by tunneling at low temperature. The calculated values agree quite well with experimental estimates. Dynamical corrections to the classical TST rate estimate were evaluated and found to be small.

  • quantum and thermal effects in h2 dissociative adsorption evaluation of free energy barriers in multidimensional quantum systems
    Physical Review Letters, 1994
    Co-Authors: Greg Mills, Hannes Jónsson
    Abstract:

    We have evaluated the sticking probability and activation energy for dissociation of ${\mathrm{H}}_{2}$ molecules on a Cu(110) surface by a Reversible Work formulation of quantum transition state theory. Feynman path integrals are used to describe the two hydrogen atoms and a few of the surface atoms, thereby including quantum effects such as tunneling and zero point energy, as well as thermal averaging. At a temperature below 600 K an onset of a quantum regime is observed as the activation energy drops by 30%.

Frederic Leroy - One of the best experts on this subject based on the ideXlab platform.

  • solid liquid Work of adhesion of coarse grained models of n hexane on graphene layers derived from the conditional Reversible Work method
    Journal of Chemical Physics, 2015
    Co-Authors: Vikram Reddy Ardham, Gregor Deichmann, Nico F A Van Der Vegt, Frederic Leroy
    Abstract:

    We address the question of how reducing the number of degrees of freedom modifies the interfacial thermodynamic properties of heterogeneous solid-liquid systems. We consider the example of n-hexane interacting with multi-layer graphene which we model both with fully atomistic and coarse-grained (CG) models. The CG models are obtained by means of the conditional Reversible Work (CRW) method. The interfacial thermodynamics of these models is characterized by the solid-liquid Work of adhesion WSL calculated by means of the dry-surface methodology through molecular dynamics simulations. We find that the CRW potentials lead to values of WSL that are larger than the atomistic ones. Clear understanding of the relationship between the structure of n-hexane in the vicinity of the surface and WSL is elucidated through a detailed study of the energy and entropy components of WSL. We highlight the crucial role played by the solid-liquid energy fluctuations. Our approach suggests that CG potentials should be designed in such a way that they preserve the range of solid-liquid interaction energies, but also their fluctuations in order to preserve the reference atomistic value of WSL. Our study thus opens perspectives into deriving CG interaction potentials that preserve the thermodynamics of solid-liquid contacts and will find application in studies that intend to address materials driven by interfaces.

  • dry surface simulation method for the determination of the Work of adhesion of solid liquid interfaces
    Langmuir, 2015
    Co-Authors: Frederic Leroy, Florian Mullerplathe
    Abstract:

    We introduce a methodology, referred to as the dry-surface method, to calculate the Work of adhesion of heterogeneous solid–liquid interfaces by molecular simulation. This method employs a straightforward thermodynamic integration approach to calculate the Work of adhesion as the Reversible Work to turn off the attractive part of the actual solid–liquid interaction potential. It is formulated in such a way that it may be used either to evaluate the ability of force fields to reproduce reference values of the Work of adhesion or to optimize force-field parameters with reference values of the Work of adhesion as target quantities. The methodology is tested in the case of water on a generic model of nonpolar substrates with the structure of gold. It is validated through a quantitative comparison to phantom-wall calculations and against a previous characterization of the thermodynamics of the gold–water interface. It is found that the Work of adhesion of water on nonpolar substrates is a nonlinear function of...

David S Corti - One of the best experts on this subject based on the ideXlab platform.

  • extension of scaled particle theory to inhomogeneous hard particle fluids iv cavity growth at any distance relative to a planar hard wall
    Physical Review E, 2011
    Co-Authors: Daniel W Siderius, David S Corti
    Abstract:

    A completely generalized version of an inhomogeneous scaled particle theory (I-SPT) for hard particle fluids confined by hard walls is presented, whereby the Reversible Work of cavity insertion can be determined for a cavity of any radius located at any distance from the hard wall. New exact and approximate conditions on the central function Ḡ of I-SPT are developed, where Ḡ is related to the average value of the anisotropic density of hard-sphere centers at the surface of the cavity. The predictions of the Work of insertion and the form of Ḡ are quite accurate up to moderate bulk densities as compared to molecular simulation results. The accuracy of I-SPT begins to decline at high densities, due to limitations of certain needed approximations required for a complete description of Ḡ. Finally, interesting insights into the origin of depletion effects between a hard-sphere solute and the hard wall are generated via this version of I-SPT. The oscillatory nature of depletion forces, exhibiting both attractive and repulsive domains, is found to arise from the interplay between bulk SPT and I-SPT relations.

  • homogeneous bubble nucleation in stretched fluids cavity formation in the superheated lennard jones liquid
    Industrial & Engineering Chemistry Research, 2002
    Co-Authors: Sudeep N Punnathanam, David S Corti
    Abstract:

    A consideration of various ideas set forth within the scaled particle theory of hard particle fluids, which are also applicable to systems whose particles interact via attractive potentials, suggests that cavity formation plays an important role in the molecular mechanism of the liquid-to-vapor transition. Umbrella sampling Monte Carlo simulations are used to calculate the Reversible Work of forming cavities of various sizes within the superheated Lennard-Jones liquid maintained at several negative pressures. A critical cavity size is found to occur, beyond which the liquid would phase separate if not for a density constraint that is applied during the simulation. The Work of forming this critically sized cavity and its radius is found to decrease as the liquid approaches the spinodal. A critical cavity size is also found for the superheated liquid at positive pressures. The focus on cavity growth in superheated liquids amounts to a new way of studying bubble nucleation and should lead to an improved molecular-based understanding of the kinetics of first-order phase transitions in liquids.

David Chandler - One of the best experts on this subject based on the ideXlab platform.

  • transition path sampling and the calculation of rate constants
    Journal of Chemical Physics, 1998
    Co-Authors: Christoph Dellago, Peter G Bolhuis, Felix S Csajka, David Chandler
    Abstract:

    We have developed a method to study transition pathways for rare events in complex systems. The method can be used to determine rate constants for transitions between stable states by turning the calculation of reactive flux correlation functions into the computation of an isomorphic Reversible Work. In contrast to previous dynamical approaches, the method relies neither on prior knowledge nor on explicit specification of transition states. Rather, it provides an importance sampling from which transition states can be characterized statistically. A simple model is analyzed to illustrate the methodology.

Lu Huixia - One of the best experts on this subject based on the ideXlab platform.

  • Microscopic interactions of melatonin, serotonin and tryptophan with zwitterionic phospholipid membranes
    'MDPI AG', 2021
    Co-Authors: Martí Rabassa Jordi, Lu Huixia
    Abstract:

    The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simu- lations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this Work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the mem- brane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phos- pholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10–20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from Reversible Work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10^(-7) cm^2/s for the cholesterol-free and cholesterol-rich setups.Postprint (author's final draft

  • Exploring free-energy landscapes and microscopic interactions of selected small-molecules and proteins with cell membranes
    Universitat Politècnica de Catalunya, 2020
    Co-Authors: Lu Huixia
    Abstract:

    The present Thesis is devoted to the study of the physical-chemical properties of selected small-molecules (such as amino-acids like tryptophan or hormones like melatonin) and proteins (such as KRAS-4B) absorbed in model lipid bilayers located at physiological environments. Since in such conditions biological membranes composed of phospholipids and cholesterol are surrounded by electrolyte solutions, understanding the interactions of the small molecule or protein with the surrounding phospholipids, cholesterol, water and all sorts of ion species is a topic of great fundamental importance. In particular, the present Thesis has advanced into the analysis of the structural and energetic aspects of an oncogenic protein from the RAS family, characterising the physical conditions that allow such protein to remain anchored to the cell. The findings reported in the Thesis may help to shed light in the understanding of a wide variety of cancers, with direct impact on the design of drugs or treatments useful for curation. The lipids considered in this Thesis include the saturated lipids dimyristoilphosphatidylcholine (DMPC) and dipalmytoilphosphatidylcholine (DPPC), the unsaturated lipids dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylserine(DOPS) and cholesterol. Classical molecular dynamics simulations and well-tempered metadynamics simulations have been applied in this thesis so that all considered systems have been modelled and simulated at the all-atom level, with systems containing up to 200000 atoms. Using classical molecular dynamics simulations at the microsecond time scale, we studied the microscopic structure and dynamics of the small-molecules and KRAS4B proteins, the latter in the wild-type and mutated (oncogenic) forms. The cell membrane has been always considered in the liquid crystalline phase, what in some cases required to rise the temperature of the system up to 323 K. Structural properties such as the area per lipid and thickness of the membrane, density profiles, deuterium-order parameters, orientational distributions and the extent of water penetration in the membrane have been analysed. Molecular self-diffusion and spectral densities of atomic species reveal a variety of time scales playing a role in membrane dynamics. The physical meaning of all spectral features from lipid atomic sites is analysed and correlated with experimental data. Most relevant have been the location of individual sites of binding of probes at the interface of the membrane. Finally, using Reversible Work techniques, we estimated the extent of free energy required to form such liaisons. By applying 1-microsecond well-tempered metadynamics simulations, we have performed systematic free energy calculations of probe binding to the membrane and water for the first time. Free energy landscapes unveil specific binding behaviour of small-molecules and proteins at phospholipid membranes. This Thesis provides a general methodology to explore such free energy landscapes at complex biological interfaces which can be extended to study other interactions of interest between molecules, peptides, proteins or drugs and charged head-groups in colloidal chemistry and biology. We further applied this methodology to study the case of a prototypical oncogenic protein (KRAS), being able to produce a wide variety of cancers. Our results from resulting free energy landscapes indicate the existence of specific hydrogen-bonding connections between parts of the protein (hypervariable region and farnesylated tail) that might be responsible of the permanent infection of healthy cells through its anchoring at the interface of the membrane.La presente Tesis doctoral está dedicada al estudio de las propiedades físico-químicas de moléculas pequeñas seleccionadas (por ejemplo aminoácidos como el triptófano u hormonas como la melatonina) y proteínas (como la KRas-4B) absorbidas en membranas celulares formadas por fosfolípidos y ubicadas en entornos fisiológicos. Dado que en estas condiciones, las membranas biológicas compuestas por fosfolípidos y colesterol están rodeadas de soluciones de electrólitos, entender las interacciones de la molécula pequeña o proteína con los fosfolípidos circundantes, el colesterol, el agua y todo tipo de especies iónicas es un tema de gran importancia fundamental. En particular, la presente Tesis se ha avanzado en el análisis de los aspectos estructurales y energéticos de una proteína oncogènica de la familia Ras, caracterizando las condiciones físicas que permiten que esta proteína se mantenga anclada a la célula. Las resultados descritos a la tesis pueden ayudar a dar luz a la comprensión de una gran variedad de cánceres, con un impacto directo en el diseño de medicamentos o tratamientos útiles para su curación. Los lípidos considerados en esta Tesis incluyen los lípidossaturados dimiristoilfosfatidilcolina y dipalmitoilfosfatidilcolina, los lípidos insaturados dioleoilfosfatidilcolina y dioleoilfosfatidilserina y el colesterol. En esta Tesis se han aplicado simulaciones de dinámica molecular clásica y simulaciones de metadinámica bien temperada, de forma que todos los sistemas considerados han estado modelizados y simulados a nivel puramente atómico, con sistemas de hasta 200000 átomos. Utilizando simulaciones clásicas de dinámica molecular (a escala 1 microsegundo), hemos estudiado la estructura y la dinámica microscópicas de las moléculas pequeñas y las proteínas KRas4B, estas últimas en formas pura y mutada (oncogénica). La membrana celular siempre se ha considerado en fase cristalina líquida, cosa que en algunos casos ha requerido aumentar la temperatura del sistema hasta 323 K. Se han calculado propiedades estructurales como por ejemplo el área por lípido y el grosor de la membrana, perfiles de densidad, parámetros de orden del deuterio, distribuciones orientacionals y el alcance de la penetración del agua a la membrana. Los coeficientes de difusión moleculares y las densidades espectrales atómicas revelan una gran variedad de escalas de tiempos que tienen un papel en la dinámica de membrana. El significado físico de todas las características espectrales de los lugares atómicos lipídicos se ha analizado y correlacionado con datos experimentales. El más relevante ha sido el hallazgo de la ubicación de lugares individuales de enlace de las varias sondas (pequeñas moléculas y proteínas) a la interfaz de la membrana. Finalmente, utilizando técnicas de trabajo Reversible, se ha podido estimar la cantidad de energía libre necesaria para formar estos enlaces. Mediante la aplicación de simulaciones de metadinámica bien temperada de 1 microsegundo, hemos realizado por primera vez cálculos de energía libre sistemática de la unión de las varias sondas a la membrana y al agua. Las superficies de energía libre muestran un comportamiento específico de los enlaces de moléculas pequeñas y proteínas a las membranas fosfolípidiques. Esta Tesis proporciona una metodología general para explorar superficies de energía libre en interfaces biológicas complejas que se pueden ampliar para estudiar otras interacciones de interés entre moléculas, péptidos, proteínas o fármacos y membranas en Química y Biología coloidal. También hemos aplicado esta metodología para estudiar el caso de una proteína oncogènica prototípica (KRas), que se considera responsable de una gran variedad de cánceres. Nuestros resultados en superficies de energía libre indican la existencia de conexiones específicas de enlace de hidrógeno entre partes de la proteína (región hipervariabley cola farnesilada) que podrían ser responsables de la infección permanente de células sanas a través de su anclaje a la interfaz de la membrana

  • Exploring free-energy landscapes and microscopic interactions of selected small-molecules and proteins wih cell membranes
    Universitat Politècnica de Catalunya, 2020
    Co-Authors: Lu Huixia
    Abstract:

    The present Thesis is devoted to the study of the physical-chemical properties of selected small-molecules (such as amino-acids like tryptophan or hormones like melatonin) and proteins (such as KRAS-4B) absorbed in model lipid bilayers located at physiological environments. Since in such conditions biological membranes composed of phospholipids and cholesterol are surrounded by electrolyte solutions, understanding the interactions of the small molecule or protein with the surrounding phospholipids, cholesterol, water and all sorts of ion species is a topic of great fundamental importance. In particular, the present Thesis has advanced into the analysis of the structural and energetic aspects of an oncogenic protein from the RAS family, characterising the physical conditions that allow such protein to remain anchored to the cell. The findings reported in the Thesis may help to shed light in the understanding of a wide variety of cancers, with direct impact on the design of drugs or treatments useful for curation. The lipids considered in this Thesis include the saturated lipids dimyristoilphosphatidylcholine (DMPC) and dipalmytoilphosphatidylcholine (DPPC), the unsaturated lipids dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylserine(DOPS) and cholesterol. Classical molecular dynamics simulations and well-tempered metadynamics simulations have been applied in this thesis so that all considered systems have been modelled and simulated at the all-atom level, with systems containing up to 200000 atoms. Using classical molecular dynamics simulations at the microsecond time scale, we studied the microscopic structure and dynamics of the small-molecules and KRAS4B proteins, the latter in the wild-type and mutated (oncogenic) forms. The cell membrane has been always considered in the liquid crystalline phase, what in some cases required to rise the temperature of the system up to 323 K. Structural properties such as the area per lipid and thickness of the membrane, density profiles, deuterium-order parameters, orientational distributions and the extent of water penetration in the membrane have been analysed. Molecular self-diffusion and spectral densities of atomic species reveal a variety of time scales playing a role in membrane dynamics. The physical meaning of all spectral features from lipid atomic sites is analysed and correlated with experimental data. Most relevant have been the location of individual sites of binding of probes at the interface of the membrane. Finally, using Reversible Work techniques, we estimated the extent of free energy required to form such liaisons. By applying 1-microsecond well-tempered metadynamics simulations, we have performed systematic free energy calculations of probe binding to the membrane and water for the first time. Free energy landscapes unveil specific binding behaviour of small-molecules and proteins at phospholipid membranes. This Thesis provides a general methodology to explore such free energy landscapes at complex biological interfaces which can be extended to study other interactions of interest between molecules, peptides, proteins or drugs and charged head-groups in colloidal chemistry and biology. We further applied this methodology to study the case of a prototypical oncogenic protein (KRAS), being able to produce a wide variety of cancers. Our results from resulting free energy landscapes indicate the existence of specific hydrogen-bonding connections between parts of the protein (hypervariable region and farnesylated tail) that might be responsible of the permanent infection of healthy cells through its anchoring at the interface of the membrane.La presente Tesis doctoral está dedicada al estudio de las propiedades físico-químicas de moléculas pequeñas seleccionadas (por ejemplo aminoácidos como el triptófano u hormonas como la melatonina) y proteínas (como la KRas-4B) absorbidas en membranas celulares formadas por fosfolípidos y ubicadas en entornos fisiológicos. Dado que en estas condiciones, las membranas biológicas compuestas por fosfolípidos y colesterol están rodeadas de soluciones de electrólitos, entender las interacciones de la molécula pequeña o proteína con los fosfolípidos circundantes, el colesterol, el agua y todo tipo de especies iónicas es un tema de gran importancia fundamental. En particular, la presente Tesis se ha avanzado en el análisis de los aspectos estructurales y energéticos de una proteína oncogènica de la familia Ras, caracterizando las condiciones físicas que permiten que esta proteína se mantenga anclada a la célula. Las resultados descritos a la tesis pueden ayudar a dar luz a la comprensión de una gran variedad de cánceres, con un impacto directo en el diseño de medicamentos o tratamientos útiles para su curación. Los lípidos considerados en esta Tesis incluyen los lípidossaturados dimiristoilfosfatidilcolina y dipalmitoilfosfatidilcolina, los lípidos insaturados dioleoilfosfatidilcolina y dioleoilfosfatidilserina y el colesterol. En esta Tesis se han aplicado simulaciones de dinámica molecular clásica y simulaciones de metadinámica bien temperada, de forma que todos los sistemas considerados han estado modelizados y simulados a nivel puramente atómico, con sistemas de hasta 200000 átomos. Utilizando simulaciones clásicas de dinámica molecular (a escala 1 microsegundo), hemos estudiado la estructura y la dinámica microscópicas de las moléculas pequeñas y las proteínas KRas4B, estas últimas en formas pura y mutada (oncogénica). La membrana celular siempre se ha considerado en fase cristalina líquida, cosa que en algunos casos ha requerido aumentar la temperatura del sistema hasta 323 K. Se han calculado propiedades estructurales como por ejemplo el área por lípido y el grosor de la membrana, perfiles de densidad, parámetros de orden del deuterio, distribuciones orientacionals y el alcance de la penetración del agua a la membrana. Los coeficientes de difusión moleculares y las densidades espectrales atómicas revelan una gran variedad de escalas de tiempos que tienen un papel en la dinámica de membrana. El significado físico de todas las características espectrales de los lugares atómicos lipídicos se ha analizado y correlacionado con datos experimentales. El más relevante ha sido el hallazgo de la ubicación de lugares individuales de enlace de las varias sondas (pequeñas moléculas y proteínas) a la interfaz de la membrana. Finalmente, utilizando técnicas de trabajo Reversible, se ha podido estimar la cantidad de energía libre necesaria para formar estos enlaces. Mediante la aplicación de simulaciones de metadinámica bien temperada de 1 microsegundo, hemos realizado por primera vez cálculos de energía libre sistemática de la unión de las varias sondas a la membrana y al agua. Las superficies de energía libre muestran un comportamiento específico de los enlaces de moléculas pequeñas y proteínas a las membranas fosfolípidiques. Esta Tesis proporciona una metodología general para explorar superficies de energía libre en interfaces biológicas complejas que se pueden ampliar para estudiar otras interacciones de interés entre moléculas, péptidos, proteínas o fármacos y membranas en Química y Biología coloidal. También hemos aplicado esta metodología para estudiar el caso de una proteína oncogènica prototípica (KRas), que se considera responsable de una gran variedad de cánceres. Nuestros resultados en superficies de energía libre indican la existencia de conexiones específicas de enlace de hidrógeno entre partes de la proteína (región hipervariabley cola farnesilada) que podrían ser responsables de la infección permanente de células sanas a través de su anclaje a la interfaz de la membrana.Postprint (published version