Simulation of a Particle Domain in a Continuum, Fluctuating Hydrodynamics Reservoir.

In molecular simulation and fluid mechanics, the coupling of a particle domain with a continuum representation of its embedding environment is an ongoing challenge. In this Letter, we show a novel approach where the latest version of the adaptive resolution scheme (AdResS), with noninteracting tracers as particles' reservoir, is combined with a fluctuating hydrodynamics (FHD) solver. The resulting algorithm, supported by a solid mathematical model, allows for a physically consistent exchange of matter and energy between the particle domain and its fluctuating continuum reservoir. Numerical tests are performed to show the validity of the algorithm. Differently from previous algorithms of the same kind, the current approach allows for simulations where, in addition to density fluctuations, also thermal fluctuations can be accounted for, thus large complex molecular systems, as, for example, hydrated biological membranes in a thermal field, can now be efficiently treated.

Path Integral Molecular Dynamics of Liquid Water in a Mean-Field Particle Reservoir.

We present a simulation scheme for path integral simulation of molecular liquids where a small open region is embedded in a large reservoir of non interacting point-particles. The scheme is based on the latest development of the adaptive resolution technique AdResS and allows for the space-dependent change of molecular resolution from a path integral representation with 120 degrees of freedom to a point particle that does not interact with other molecules and vice versa. The method is applied to liquid water and implies a sizable gain regarding the request of computational resources compared to full path integral simulations. Given the role of water as universal solvent with a specific hydrogen bonding network, the path integral treatment of water molecules is important to describe the quantum effects of hydrogen atoms' delocalization in space on the hydrogen bonding network. The method presented here implies feasible computational efforts compared to full path integral simulations of liquid water which, on large scales, are often prohibitive.

Nuclear quantum effects in fullerene-fullerene aggregation in water.

We studied the effects of the quantum delocalization in space of the hydrogen atoms of water in the aggregation process of two fullerene molecules. We considered a case using a purely repulsive water-fullerene interaction, as such a situation has shown that water-mediated effects play a key role in the aggregation process. This study becomes feasible, at a reduced computational price, by combining the path integral (PI) molecular dynamics (MD) method with a recently developed open-system MD technique. Specifically, only the mandatory solvation shell of the two fullerene molecules was considered at full quantum resolution, while the rest of the system was represented as a mean-field macroscopic reservoir of particles and energy. Our results showed that the quantum nature of the hydrogen atoms leads to a sizable difference in the curve of the free energy of aggregation; that is, that nuclear quantum effects play a relevant role.

From adaptive resolution to molecular dynamics of open systems.

ABSTRACT: We provide an overview of the Adaptive Resolution Simulation method (AdResS) based on discussing its basic principles and presenting its current numerical and theoretical developments. Examples of applications to systems of interest to soft matter, chemical physics, and condensed matter illustrate the method's advantages and limitations in its practical use and thus settle the challenge for further future numerical and theoretical developments.

Investigation of water-mediated intermolecular interactions with the adaptive resolution simulation technique.

We use the adaptive resolution simulation (AdResS) technique to estimate the region in space where water-mediated effects in molecule-molecule interactions are relevant. AdResS is employed to identify the region around the solute (solvation shell) where the atomistic details of the hydrogen bonding network are relevant while outside water plays the role of a thermodynamic bath that can be described at simplified macroscopic level. The consequence is that for the interaction of two solutes the intermolecular distance at which water mediated effects start to be relevant is represented by the sum of the radii of the two respective solvation shells identified via AdResS. The hypothesis formulated above will be proven by calculating the solute-solute potential of mean force for different solutes. As test molecules we use amino acids derived from fragments of the FCHo2-F-BAR domain protein; this choice stems from the fact that the current results, beside proving the technical capability of AdResS in this context, may provide data for future actual coarse-grained models.

On the formalization of asynchronous first passage algorithms.

Formalization of first passage schemes is revisited, and the emerging conceptual contradiction is underlined. We then show why, despite such a contradiction, the numerical results are not explicitly affected. Through a different formalization of the problem, we recast the current principles of the algorithm in a more solid conceptual framework and numerical evidence gives further justification to our claims.

The physics of open systems for the simulation of complex molecular environments in soft matter.

Molecular dynamics (MD) has become one of the most powerful tools of investigation in soft matter. Despite such success, simulations of large molecular environments are mostly run using the approximation of closed systems without the possibility of exchange of matter. Due to the molecular complexity of soft matter systems, an optimal simulation strategy would require the application of concurrent multiscale resolution approaches such that each part of a large system can be considered as an open subsystem at a high resolution embedded in a large coarser reservoir of energy and particles. This paper discusses the current capability and the future perspectives of multiscale adaptive resolution MD methods to satisfy the conceptual principles of open systems and to perform simulations of complex molecular environments in soft matter.

Adaptive resolution molecular dynamics technique: Down to the essential.

We investigate the role of the thermodynamic (TD) force as an essential and sufficient technical ingredient for an efficient and accurate adaptive resolution algorithm. Such a force applied in the coupling region of an adaptive resolution molecular dynamics setup assures thermodynamic equilibrium between atomistically resolved and coarse-grained regions, allowing the proper exchange of molecules. We numerically prove that indeed for systems as relevant as liquid water and 1,3-dimethylimidazolium chloride ionic liquid, the combined action of the TD force and thermostat allows for computationally efficient and numerically accurate simulations, beyond the current capabilities of adaptive resolution setups, which employ switching functions in the coupling region.

Path integral-GC-AdResS simulation of a large hydrophobic solute in water: a tool to investigate the interplay between local microscopic structures and quantum delocalization of atoms in space.

We perform large scale quantum (path integral) molecular dynamics simulations of a C60-like molecule in water. The path integral (PI) technique allows for the description of the delocalization of atoms in space and of its consequences on the structure and dynamics of the hydrogen bonding network around the solute. We then employ the adaptive resolution method GC-AdResS, which unambiguously defines the essential (necessary) degrees of freedom required for a certain property, to analyze the locality of the water structure around the solute. We show that the feature of locality is independent of the use of a quantum or classical model of water. However the water structure around the solute obtained from classical simulations is more ordered and rigid than the structure found in quantum simulations. With this study we mainly intend to show that GC-AdResS, besides its computational efficiency, can be used as a powerful tool of multiscale analysis; this capability, in turn, can be used to speculate about processes at larger scales. We make an example, whose current validity is restricted to the molecular models specifically used, regarding the possible role of quantum effects in the aggregation of fullerene-like molecules in water.

Towards open boundary molecular dynamics simulation of ionic liquids.

We extend the use of the adaptive resolution (AdResS) method in its grand canonical-like version (GC-AdResS) to the molecular dynamics simulation of 1,3-dimethylimidazolium chloride. We show that the partitioning of the total system in a subsystem of interest with atomistic details and a reservoir of coarse-grained particles leads to satisfactory results. The challenging aspect of this study, compared to previous AdResS simulations, is the presence of charged particles and the necessity of addressing the question about the minimal physical input needed to model the coarse-grained particles in the reservoir. We propose two different approaches and show that in both cases they are sufficient to capture the decisive physical characteristics that allow a valid system-reservoir coupling. The technically satisfactory results pave the way for the multiscale analysis of ionic liquids and truly open boundary molecular simulations.

Adaptive molecular resolution approach in Hamiltonian form: An asymptotic analysis.

Adaptive molecular resolution approaches in molecular dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer (transition) region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined, and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. Such conditions show that molecular simulations in the current computational implementation require systems of large size, and thus a Hamiltonian approach such as the one proposed, at this stage, would not be practical from the numerical point of view. However, the Hamiltonian proposed provides the basis for a simplification and generalization of the numerical implementation of adaptive resolution algorithms to other molecular dynamics codes.

Formulation of Liouville's theorem for grand ensemble molecular simulations.

Liouville's theorem in a grand ensemble, that is for situations where a system is in equilibrium with a reservoir of energy and particles, is a subject that, to our knowledge, has not been explicitly treated in literature related to molecular simulation. Instead, Liouville's theorem, a central concept for the correct employment of molecular simulation techniques, is implicitly considered only within the framework of systems where the total number of particles is fixed. However, the pressing demand of applied science in treating open systems leads to the question of the existence and possible exact formulation of Liouville's theorem when the number of particles changes during the dynamical evolution of the system. The intention of this paper is to stimulate a debate about this crucial issue for molecular simulation.

Path integral molecular dynamics within the grand canonical-like adaptive resolution technique: Simulation of liquid water.

Quantum effects due to the spatial delocalization of light atoms are treated in molecular simulation via the path integral technique. Among several methods, Path Integral (PI) Molecular Dynamics (MD) is nowadays a powerful tool to investigate properties induced by spatial delocalization of atoms; however, computationally this technique is very demanding. The above mentioned limitation implies the restriction of PIMD applications to relatively small systems and short time scales. One of the possible solutions to overcome size and time limitation is to introduce PIMD algorithms into the Adaptive Resolution Simulation Scheme (AdResS). AdResS requires a relatively small region treated at path integral level and embeds it into a large molecular reservoir consisting of generic spherical coarse grained molecules. It was previously shown that the realization of the idea above, at a simple level, produced reasonable results for toy systems or simple/test systems like liquid parahydrogen. Encouraged by previous results, in this paper, we show the simulation of liquid water at room conditions where AdResS, in its latest and more accurate Grand-Canonical-like version (GC-AdResS), is merged with two of the most relevant PIMD techniques available in the literature. The comparison of our results with those reported in the literature and/or with those obtained from full PIMD simulations shows a highly satisfactory agreement.

Influence of pH and sequence in peptide aggregation via molecular simulation.

We employ a recently developed coarse-grained model for peptides and proteins where the effect of pH is automatically included. We explore the effect of pH in the aggregation process of the amyloidogenic peptide KTVIIE and two related sequences, using three different pH environments. Simulations using large systems (24 peptides chains per box) allow us to describe the formation of realistic peptide aggregates. We evaluate the thermodynamic and kinetic implications of changes in sequence and pH upon peptide aggregation, and we discuss how a minimalistic coarse-grained model can account for these details.

Chemical potential of liquids and mixtures via adaptive resolution simulation.

We employ the adaptive resolution approach AdResS, in its recently developed Grand Canonical-like version (GC-AdResS) [H. Wang, C. Hartmann, C. Schütte, and L. Delle Site, Phys. Rev. X 3, 011018 (2013)], to calculate the excess chemical potential, µ(ex), of various liquids and mixtures. We compare our results with those obtained from full atomistic simulations using the technique of thermodynamic integration and show a satisfactory agreement. In GC-AdResS, the procedure to calculate µ(ex) corresponds to the process of standard initial equilibration of the system; this implies that, independently of the specific aim of the study, µ(ex), for each molecular species, is automatically calculated every time a GC-AdResS simulation is performed.

Exploring the Conformational Dynamics of Alanine Dipeptide in Solution Subjected to an External Electric Field: A Nonequilibrium Molecular Dynamics Simulation.

In this paper, we investigate the conformational dynamics of alanine dipeptide under an external electric field by nonequilibrium molecular dynamics simulation. We consider the case of a constant and of an oscillatory field. In this context, we propose a procedure to implement the temperature control, which removes the irrelevant thermal effects of the field. For the constant field different time-scales are identified in the conformational, dipole moment, and orientational dynamics. Moreover, we prove that the solvent structure only marginally changes when the external field is switched on. In the case of oscillatory field, the conformational changes are shown to be as strong as in the previous case, and nontrivial nonequilibrium circular paths in the conformation space are revealed by calculating the integrated net probability fluxes.

Multiscale molecular modeling.

We review the basic theoretical principles of the adaptive resolution simulation scheme (AdResS). This method allows to change molecular resolution on-the-fly during a simulation by changing the number of degrees of freedom in specific regions of space where the required resolution is higher than in the rest of the system. We also report about recent extensions of the method to the continuum and quantum regimes.

Autocatalytic and cooperatively stabilized dissociation of water on a stepped platinum surface.

Water-metal interfaces are ubiquitous and play a key role in many chemical processes, from catalysis to corrosion. Whereas water adlayers on atomically flat transition metal surfaces have been investigated in depth, little is known about the chemistry of water on stepped surfaces, commonly occurring in realistic situations. Using first-principles simulations, we study the adsorption of water on a stepped platinum surface. We find that water adsorbs preferentially at the step edge, forming linear clusters or chains, stabilized by the cooperative effect of chemical bonds with the substrate and hydrogen bonds. In contrast with their behavior on flat Pt, at steps water molecules dissociate, forming mixed hydroxyl/water structures, through an autocatalytic mechanism promoted by H-bonding. Nuclear quantum effects contribute to stabilize partially dissociated cluster and chains. Together with the recently demonstrated behavior of water chains adsorbed on stepped Pt surfaces to transfer protons via thermally activated hopping, these findings make these systems viable candidates for proton wires.

Derivation of coarse grained models for multiscale simulation of liquid crystalline phase transitions.

We present a systematic derivation of a coarse grained (CG) model for molecular dynamics (MD) simulations of a liquid crystalline (LC) compound containing an azobenzene mesogen. The model aims at a later use in a multiscale modeling approach to study liquid crystalline phase transitions that are (photo)induced by the trans/cis photoisomerization of the mesogen. One of the major challenges in the coarse graining process is the development of models that are for a given chemical system structurally consistent with for example an all-atom reference model and reproduce relevant thermodynamic properties such as the LC phase behavior around the state point of interest. The reduction of number of degrees of freedom makes the resulting coarse models by construction state point dependent; that is, they cannot easily be transferred to a range of temperatures, densities, system compositions, etc. These are significant challenges, in particular if one wants to study LC phase transitions (thermally or photoinduced). In the present paper we show how one can systematically derive a CG model for a LC molecule that is highly consistent with an atomistic description by choosing an appropriate state point for the reference simulation. The reference state point is the supercooled liquid just below the smectic-isotropic phase transition which is characterized by a high degree of local nematic order while being overall isotropic. With the resulting CG model it is possible to switch between the atomistic and the CG levels (and vice versa) in a seamless manner maintaining values of all the relevant order parameters which describe the smectic A (smA) state. This model will allow us in the future to link large length scale and long time scale CG simulations of the LC state with chemically accurate QM/MM simulations of the photoisomerization process.

Ionic liquids studied across different scales: a computational perspective.

For theoreticians, ionic liquids represent a major challenge. This is due to the fact that intermolecular interactions are particularly strong because of ionic liquids' ionicity. This, in turn, causes a subtle interplay between different scales which is encoded in the measured macro- and mesoscopic properties and also in the molecular electrostatic characteristics. Therefore, force fields have to describe the microscopic processes correctly in order to reproduce macroscopic properties accurately over a large range of state variables. Herein, imidazolium-based ionic liquids were studied at different scales, going from the detailed quantum electronic scale to the classical atomistic scale. It is indicated how the information gained at each level could be used for the other scales. In particular, the issue of deriving suitable partial charges for use in classical force fields is addressed. The Blöchl method was employed to generate partial charges reproducing the multipole distribution accurately for bulk systems. This led naturally to absolute ionic charges of less than /l e/, i.e., charge scaling. So, the monopole structure of the herein introduced force field mimics the quantum chemical behaviour observed in the liquid phase. This led to a substantial improvement in the description of dynamical properties of immediate experimental interest, such as electric conductivity. For further insight, the electric dipole moment of the ions was taken as physical indicator of their electronic structure. The electric dipole moment was found to fluctuate strongly and to depend on polarisation. Hence, our scale-combined study offers a gateway to rational design of models, based on the relevant underlying physics rather than on mere numerical parameterisation, and thereby to (possibly) more direct physical interpretation of experimental results.