The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Pablo G Debenedetti - One of the best experts on this subject based on the ideXlab platform.
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computational investigation of surface freezing in a Molecular Model of water
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Water freezes in a wide variety of low-temperature environments, from meteors and atmospheric clouds to soil and biological cells. In nature, ice usually nucleates at or near interfaces, because homogenous nucleation in the bulk can only be observed at deep supercoolings. Although the effect of proximal surfaces on freezing has been extensively studied, major gaps in understanding remain regarding freezing near vapor–liquid interfaces, with earlier experimental studies being mostly inconclusive. The question of how a vapor–liquid interface affects freezing in its vicinity is therefore still a major open question in ice physics. Here, we address this question computationally by using the forward-flux sampling algorithm to compute the nucleation rate in a freestanding nanofilm of supercooled water. We use the TIP4P/ice force field, one of the best existing Molecular Models of water, and observe that the nucleation rate in the film increases by seven orders of magnitude with respect to bulk at the same temperature. By analyzing the nucleation pathway, we conclude that freezing in the film initiates not at the surface, but within an interior region where the formation of double-diamond cages (DDCs) is favored in comparison with the bulk. This, in turn, facilitates freezing by favoring the formation of nuclei rich in cubic ice, which, as demonstrated by us earlier, are more likely to grow and overcome the nucleation barrier. The films considered here are ultrathin because their interior regions are not truly bulk-like, due to their subtle structural differences with the bulk.
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direct calculation of ice homogeneous nucleation rate for a Molecular Model of water
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure, and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained Models of water. For Molecular Models, only indirect estimates have been obtained, e.g., by assuming the validity of classical nucleation theory. We use a path sampling approach to perform, to our knowledge, the first direct rate calculation of homogeneous nucleation of ice in a Molecular Model of water. We use TIP4P/Ice, the most accurate among existing Molecular Models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over because the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a Molecular explanation for the earlier experimental and computational observations of the preference for cubic ice in the literature.
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direct calculation of ice homogeneous nucleation rate for a Molecular Model of water
arXiv: Chemical Physics, 2015Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained Models of wate. For Molecular Models, only indirect estimates have been obtained, e.g. by assuming the validity of classical nucleation theory. We use a path sampling approach to perform the first direct rate calculation of homogeneous nucleation of ice in a Molecular Model of water. We use TIP4P/Ice, the most accurate among existing Molecular Models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over since the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a Molecular explanation to the earlier experimental and computational observations of the preference for cubic ice in the literature.
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metastable liquid liquid transition in a Molecular Model of water
Nature, 2014Co-Authors: Jeremy C Palmer, Fausto Martelli, Athanassios Z Panagiotopoulos, Pablo G DebenedettiAbstract:A stable crystal phase and two metastable liquid phases of the ST2 Model of water exist at the same deeply supercooled condition, and the two liquids undergo a first-order liquid–liquid transition that meets stringent thermodynamic criteria. Water's anomalous physical properties become markedly enhanced upon supercooling below the freezing point and even seem to diverge towards infinity at around 228 K. Two papers in this issue use contrasting techniques to study this little-explored 'no-man's land' of water where extremely fast ice formation has prohibited measurements of the liquid state. Jonas Sellberg et al. use femtosecond X-ray laser pulses to measure bulk liquid water structure in droplets evaporatively cooled to 227 K. Even at this temperature some droplets remained liquid on a millisecond timescale. Pushing this technique further can shed light on controversial scenarios that aim to describe and explain the many anomalous properties of water. Jeremy Palmer et al. use six advanced computational methods to demonstrate the existence of two metastable liquid phases of ST2 water at the same deeply supercooled condition, undergoing a liquid–liquid transition that meets stringent thermodynamic criteria and could explain the behavior of water in this regime. Liquid water’s isothermal compressibility1 and isobaric heat capacity2, and the magnitude of its thermal expansion coefficient3, increase sharply on cooling below the equilibrium freezing point. Many experimental4,5,6,7,8, theoretical9,10,11 and computational12,13 studies have sought to understand the Molecular origin and implications of this anomalous behaviour. Of the different theoretical scenarios9,14,15 put forward, one posits the existence of a first-order phase transition that involves two forms of liquid water and terminates at a critical point located at deeply supercooled conditions9,12. Some experimental evidence is consistent with this hypothesis4,16, but no definitive proof of a liquid–liquid transition in water has been obtained to date: rapid ice crystallization has so far prevented decisive measurements on deeply supercooled water, although this challenge has been overcome recently16. Computer simulations are therefore crucial for exploring water’s structure and behaviour in this regime, and have shown13,17,18,19,20,21 that some water Models exhibit liquid–liquid transitions and others do not. However, recent work22,23 has argued that the liquid–liquid transition has been mistakenly interpreted, and is in fact a liquid–crystal transition in all atomistic Models of water. Here we show, by studying the liquid–liquid transition in the ST2 Model of water24 with the use of six advanced sampling methods to compute the free-energy surface, that two metastable liquid phases and a stable crystal phase exist at the same deeply supercooled thermodynamic condition, and that the transition between the two liquids satisfies the thermodynamic criteria of a first-order transition25. We follow the rearrangement of water’s coordination shell and topological ring structure along a thermodynamically reversible path from the low-density liquid to cubic ice26. We also show that the system fluctuates freely between the two liquid phases rather than crystallizing. These findings provide unambiguous evidence for a liquid–liquid transition in the ST2 Model of water, and point to the separation of time scales between crystallization and relaxation as being crucial for enabling it.
Jurgen Bajorath - One of the best experts on this subject based on the ideXlab platform.
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evaluation of Molecular Model based discovery of ecto 5 nucleotidase inhibitors on the basis of x ray structures
Journal of Cheminformatics, 2014Co-Authors: Norbert Furtmann, Jurgen BajorathAbstract:Ecto-5’-nucleotidase (e5NT) belongs to the family of metallophosphoesterases, hydrolyses AMP to adenosine, and is a regulator of the adenosine signaling pathway [1]. It has been shown, that free adenosine is involved in various diseases and cancer progression [2,3]. In a previous study, a Molecular Model of e5NT has been created and used for the identification of new sulfonamide inhibitors [4]. Recently, X-ray structures of human e5NT in complex with different inhibitors were published [5]. This made it possible to reevaluate the Model building and virtual screening efforts in detail. An extensive analysis of the comparative e5NT Model, built using a bacterial enzyme in the presence of 35% sequence identity as a template, showed that the Model was topologically correct and had high accuracy within the active site region. Comparative docking studies were carried out to explore inhibitor binding characteristics within the X-ray structure and the Model. The results provided plausible explanations for the successful identification of new e5NT inhibitors by Model-based virtual screening and highlighted important parameters [6].
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evaluation of Molecular Model based discovery of ecto 5 nucleotidase inhibitors on the basis of x ray structures
Bioorganic & Medicinal Chemistry, 2013Co-Authors: Norbert Furtmann, Jurgen BajorathAbstract:Abstract The enzyme ecto-5′-nucleotidase (e5NT, CD73), a metallophosphoesterase, is a critical component of adenosine metabolism and signaling and implicated in different disease states. Therefore, attempts have been made to discover inhibitors of e5NT. For example, a virtual screening study using a Molecular Model of the enzyme has led to the identification of a new series of sulfonamide-containing e5NT inhibitors. The recent availability of several X-ray structures of human e5NT in complex with inhibitors has made it possible to re-evaluate this Model building and virtual screening effort. We have assessed the quality of the Model in detail and analyzed the question why it was possible to identify a new series of inhibitors on the basis of Model-based docking calculations. The Model utilized for virtual screening was found to be topologically correct and approach experimental accuracy in the active site region. Two key features within the active site were identified as major determinants for the successfully identification of inhibitors. Taken together, the results rationalize the computer-aided discovery of sulfonamide inhibitors of e5NT and provide further support for the use of carefully built protein Models for virtual screening.
Amir Hajiakbari - One of the best experts on this subject based on the ideXlab platform.
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computational investigation of surface freezing in a Molecular Model of water
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Water freezes in a wide variety of low-temperature environments, from meteors and atmospheric clouds to soil and biological cells. In nature, ice usually nucleates at or near interfaces, because homogenous nucleation in the bulk can only be observed at deep supercoolings. Although the effect of proximal surfaces on freezing has been extensively studied, major gaps in understanding remain regarding freezing near vapor–liquid interfaces, with earlier experimental studies being mostly inconclusive. The question of how a vapor–liquid interface affects freezing in its vicinity is therefore still a major open question in ice physics. Here, we address this question computationally by using the forward-flux sampling algorithm to compute the nucleation rate in a freestanding nanofilm of supercooled water. We use the TIP4P/ice force field, one of the best existing Molecular Models of water, and observe that the nucleation rate in the film increases by seven orders of magnitude with respect to bulk at the same temperature. By analyzing the nucleation pathway, we conclude that freezing in the film initiates not at the surface, but within an interior region where the formation of double-diamond cages (DDCs) is favored in comparison with the bulk. This, in turn, facilitates freezing by favoring the formation of nuclei rich in cubic ice, which, as demonstrated by us earlier, are more likely to grow and overcome the nucleation barrier. The films considered here are ultrathin because their interior regions are not truly bulk-like, due to their subtle structural differences with the bulk.
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direct calculation of ice homogeneous nucleation rate for a Molecular Model of water
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure, and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained Models of water. For Molecular Models, only indirect estimates have been obtained, e.g., by assuming the validity of classical nucleation theory. We use a path sampling approach to perform, to our knowledge, the first direct rate calculation of homogeneous nucleation of ice in a Molecular Model of water. We use TIP4P/Ice, the most accurate among existing Molecular Models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over because the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a Molecular explanation for the earlier experimental and computational observations of the preference for cubic ice in the literature.
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direct calculation of ice homogeneous nucleation rate for a Molecular Model of water
arXiv: Chemical Physics, 2015Co-Authors: Amir Hajiakbari, Pablo G DebenedettiAbstract:Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained Models of wate. For Molecular Models, only indirect estimates have been obtained, e.g. by assuming the validity of classical nucleation theory. We use a path sampling approach to perform the first direct rate calculation of homogeneous nucleation of ice in a Molecular Model of water. We use TIP4P/Ice, the most accurate among existing Molecular Models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over since the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a Molecular explanation to the earlier experimental and computational observations of the preference for cubic ice in the literature.
Hiroaki Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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variable soft sphere Molecular Model for air species
Physics of Fluids, 1992Co-Authors: Katsuhisa Koura, Hiroaki MatsumotoAbstract:A reliable set of cross‐section parameters of the variable soft sphere (VSS) Molecular Model is determined for the Monte Carlo simulation of air species from the transport collision integrals or potential parameters provided by Cubley and Mason [Phys. Fluids 18, 1109 (1975)] over the high‐temperature range 300–15 000 K. The VSS cross‐section parameters for the inverse‐power‐law potential are also determined from the viscosity coefficients recommended by Maitland and Smith [J. Chem. Eng. Data 17, 150 (1972)] for common species in the low (20–300 K) and high (300–2000 K) temperature ranges.
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variable soft sphere Molecular Model for inverse power law or lennard jones potential
Physics of Fluids, 1991Co-Authors: Katsuhisa Koura, Hiroaki MatsumotoAbstract:The variable soft sphere (VSS) Molecular Model is introduced for both the viscosity and diffusion cross sections (coefficients) to be consistent with those of the inverse‐power‐law (IPL) or Lennard‐Jones (LJ) potential. The VSS Model has almost the same analytical and computational simplicity (computation time) as the variable hard sphere (VHS) Model in the Monte Carlo simulation of rarefied gas flows. The null‐collision Monte Carlo method is used to make comparative calculations for the Molecular diffusion in a heat‐bath gas and the normal shock wave structure in a simple gas. For the most severe test of the VSS Model for the IPL potential, the softest practical Model corresponding to the Maxwell molecule is chosen. The agreement in the Molecular diffusion and shock wave structure between the VSS Model and the IPL or LJ potential is remarkably good.
Norbert Furtmann - One of the best experts on this subject based on the ideXlab platform.
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evaluation of Molecular Model based discovery of ecto 5 nucleotidase inhibitors on the basis of x ray structures
Journal of Cheminformatics, 2014Co-Authors: Norbert Furtmann, Jurgen BajorathAbstract:Ecto-5’-nucleotidase (e5NT) belongs to the family of metallophosphoesterases, hydrolyses AMP to adenosine, and is a regulator of the adenosine signaling pathway [1]. It has been shown, that free adenosine is involved in various diseases and cancer progression [2,3]. In a previous study, a Molecular Model of e5NT has been created and used for the identification of new sulfonamide inhibitors [4]. Recently, X-ray structures of human e5NT in complex with different inhibitors were published [5]. This made it possible to reevaluate the Model building and virtual screening efforts in detail. An extensive analysis of the comparative e5NT Model, built using a bacterial enzyme in the presence of 35% sequence identity as a template, showed that the Model was topologically correct and had high accuracy within the active site region. Comparative docking studies were carried out to explore inhibitor binding characteristics within the X-ray structure and the Model. The results provided plausible explanations for the successful identification of new e5NT inhibitors by Model-based virtual screening and highlighted important parameters [6].
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evaluation of Molecular Model based discovery of ecto 5 nucleotidase inhibitors on the basis of x ray structures
Bioorganic & Medicinal Chemistry, 2013Co-Authors: Norbert Furtmann, Jurgen BajorathAbstract:Abstract The enzyme ecto-5′-nucleotidase (e5NT, CD73), a metallophosphoesterase, is a critical component of adenosine metabolism and signaling and implicated in different disease states. Therefore, attempts have been made to discover inhibitors of e5NT. For example, a virtual screening study using a Molecular Model of the enzyme has led to the identification of a new series of sulfonamide-containing e5NT inhibitors. The recent availability of several X-ray structures of human e5NT in complex with inhibitors has made it possible to re-evaluate this Model building and virtual screening effort. We have assessed the quality of the Model in detail and analyzed the question why it was possible to identify a new series of inhibitors on the basis of Model-based docking calculations. The Model utilized for virtual screening was found to be topologically correct and approach experimental accuracy in the active site region. Two key features within the active site were identified as major determinants for the successfully identification of inhibitors. Taken together, the results rationalize the computer-aided discovery of sulfonamide inhibitors of e5NT and provide further support for the use of carefully built protein Models for virtual screening.
