Steven O. Nielsen

Energy Conservation in Adaptive Hybrid Atomistic/Coarse-Grain Molecular Dynamics.

Multiscale computer simulation algorithms are required to describe complex molecular systems with events occurring over a range of time and length scales. True multiscale simulations must solve the interface, or hand-shaking, problem of coupling together different levels of description in different spatial regions of the system. If the spatial regions of different resolution move over time, or if material is allowed to flow over the inter-region boundaries, a mechanism must be introduced into the multiscale algorithm to allow material to dynamically change its representation. While such a mechanism is highly desirable in many instances, it is fraught with technical difficulties. Here, we present a molecular dynamics simulation algorithm which is multiscale in both time and space. We supplement the potential and kinetic energy expressions with auxiliary terms in order to recover the total energy as a conserved quantity, even when the total number of degrees of freedom changes during the simulation. This is crucial for a proper assessment of the quality of adaptive hybrid algorithms, and in particular, it allows us to tune the hierarchy of RESPA levels to optimize the integration scheme.

Recent progress in adaptive multiscale molecular dynamics simulations of soft matter

Understanding mesoscopic phenomena in terms of the fundamental motions of atoms and electrons poses a severe challenge for molecular simulation. This challenge is being met by multiscale modeling techniques that aim to bridge between the microscopic and mesoscopic time and length scales. In such techniques different levels of theory are combined to describe a system at a number of scales or resolutions. Here we review recent advancements in adaptive hybrid simulations, in which the different levels are used in separate spatial domains and matter can diffuse from one region to another with an accompanying resolution change. We discuss what it means to simulate such a system, and how to enact the resolution changes. We show how to construct efficient adaptive hybrid quantum mechanics/molecular mechanics (QM/MM) and atomistic/coarse grain (AA/CG) molecular dynamics methods that use an intermediate healing region to smoothly couple the regions together. This coupling is formulated to use only the native forces inherent to each region. The total energy is conserved through the use of auxiliary bookkeeping terms. Error control, and the choice of time step and healing region width, is obtained by careful analysis of the energy flow between the different representations. We emphasize the CG → AA reverse mapping problem and show how this problem is resolved through the use of rigid atomistic fragments located within each CG particle whose orientation is preconditioned for a possible resolution change through a rotational dynamics scheme. These advancements are shown to enable the adaptive hybrid multiscale molecular dynamics simulation of macromolecular soft matter systems.

Molecular dynamics study of a nanotube-binding amphiphilic helical peptide at different water/hydrophobic interfaces.

Many potential applications of single-walled carbon nanotubes (SWNTs) require that they be isolated from one another. This may be accomplished through covalent or noncovalent SWNT functionalization. The noncovalent approach preserves the intrinsic electrical, optical, and mechanical properties of SWNTs and can be achieved by dispersing SWNTs in aqueous solution using surfactants, polymers, or biomacromolecules like DNA or polypeptides. The designed amphiphilic helical peptide nano-1, which contains hydrophobic valine and aromatic phenylalanine residues for interaction with SWNTs and glutamic acid and lysine residues for water solubility, has been shown to debundle and disperse SWNTs, although the details of the peptide-SWNT interactions await elucidation. Here we use fully atomistic molecular dynamics simulations to investigate the nano-1 peptide at three different water/hydrophobic interfaces: water/oil, water/graphite, and water/SWNT. The amphiphilic nature of the peptide is characterized by its secondary structure, peptide-water hydrogen bonding, and peptide-hydrophobic surface van der Waals energy. We show that nano-1 has reduced amphiphilic character at the water/oil interface because the peptide helix penetrates into the hydrophobic phase. The peptide alpha-helix cannot match its hydrophobic face to the rigid planar graphite surface without partially unfolding. In contrast, nano-1 can curve on the SWNT surface in an alpha-helical conformation to simultaneously maximize its hydrophobic contacts with the SWNT and its hydrogen bonds with water. The molecular insight into the peptide conformation at the various hydrophobic surfaces provides guidelines for future peptide design.

Coarse-grained potential models for phenyl-based molecules: I. Parametrization using experimental data.

A coarse-grained intermolecular potential has been parametrized for phenyl-based molecules. The parametrization was accomplished by fitting to experimental thermodynamic data. Specifically, the intermolecular potentials, which were based on Lennard-Jones functional forms, were parametrized and validated using experimental surface tension, density, and partitioning data. This approach has been used herein to develop parameters for coarse-grained interaction sites that are applicable to a variety of phenyl-based molecules, including analogues of the amino acid side chains of phenylalanine and tyrosine. Comparison of the resulting coarse-grain model to atomistic simulations shows a high level of structural and thermodynamic agreement between the two models, despite the fact that no atomistic simulation data was used in the parametrization of the coarse-grain intermolecular potentials.

Parametrization and Application of a Coarse Grained Force Field for Benzene/Fullerene Interactions with Lipids

Recently, we reported new coarse grain (CG) force fields for lipids and phenyl/fullerene based molecules. Here, we developed the cross parameters necessary to unite those force fields and then applied the model to investigate the nature of benzene and C(60) interactions with lipid bilayers. The interaction parameters between the phenyl and lipid CG sites are based on experimental and all atom (AA) molecular dynamics (MD) data. The resulting force field was tested on benzene rich lipid bilayers and shown to reproduce general behavior expected from experiments. The parameters were then applied to C(60) interactions with lipid bilayers. Overall, the results showed excellent agreement with AA MD and experimental observations. In the C(60) lipid systems, the fullerenes were shown to aggregate even at the lowest concentrations investigated.

Coarse-grained potential models for phenyl-based molecules: II. Application to fullerenes.

The interaction of fullerenes with biological systems and the environment is a topic of current interest. Coarse-grained molecular dynamics (CGMD) simulations are well-suited to investigate some of the factors involved because they provide access to time and length scales that are not accessible using fully atomistic simulation methods. In the case of buckyballs (C(60)) and single-walled carbon nanotubes (SWNTs), it is necessary to parametrize a CG force field that accurately captures the balance between fullerene-fullerene and fullerene-solvent interactions. Herein, we derive CG force field parameters for C(60) and SWNTs by using the optimized benzene parameters from part I [DeVane, R.; Chiu, C.-c.; Nielsen, S. O.; Shinoda, W.; Moore, P. B.; Klein, M. L. J. Phys. Chem. B 2010, doi: 10.1021/jp9117369]. Solubility, transfer free energy, and dimerization free-energy data for C(60) and SWNTs obtained using the proposed models show excellent agreement with experimental and fully atomistic MD data. In particular, cluster analysis of C(60) aggregation in a hydrocarbon melt corroborates the force field parameters. The aggregation behavior of the present CG force field differs considerably from that of models currently in widespread use. The combined results provide a strong basis for applying this model for further large-scale MD studies involving C(60) and SWNTs.

Role of peptide-peptide interactions in stabilizing peptide-wrapped single-walled carbon nanotubes: A molecular dynamics study

Single‐walled carbon nanotubes (SWNTs) have unique properties and are projected to have a major impact in nanoscale electronics, materials science, and nanomedicine. Yet, these potential applications are hindered by the need for sample purification to separate SWNTs from each other and from metallic catalyst and amorphous carbon present in as‐synthesized samples. Common purification strategies involve dispersing SWNTs as individual tubes in aqueous solution. Towards this end, a designed helical peptide was shown to be excellent at dispersing SWNTs. However, the molecular details of the peptide‐SWNT and peptide‐peptide interactions await elucidation. Here we explore these molecular interactions using fully atomistic molecular dynamics simulations of peptide‐wrapped SWNTs. We characterize the interactions by measuring the aromatic residue‐to‐SWNT surface distance, the peptide amphiphilicity, the peptide‐SWNT crossing angle, the peptide‐SWNT contact area, the peptide helix axis‐to‐axis distance, and the inter‐peptide hydrogen bonding. We find that the peptides collectively tilt with respect to the SWNT long axis, are α‐helical, and form interpeptide hydrogen bonds through their lysine and glutamate residues, which helps to stabilize the multipeptide/SWNT complex. All hydrophobic residues interact with the SWNT and are sequestered from water. The picture that emerges from this study gives insight into subsequent peptide design.

Size-dependent hydrophobic to hydrophilic transition for nanoparticles: A molecular dynamics study

The physical properties of nanoscale materials often vary with their size, unlike the corresponding bulk material properties, which can only be changed by modifying the material composition. In particular, it is believed that hydration phenomena are length scale dependent. The manifestation of hydrophobicity over multiple length scales plays a crucial role in self-assembly processes such as protein folding and colloidal stability. In the case of particles composed of a bulk hydrophobic material, it is well known that the free energy of hydration monotonically increases with particle size. However, the size-dependent free energy of hydration for particles composed of a bulk hydrophilic material has not been studied. Here we show that the free energy of hydration is not a monotonic function of particle size, but rather, changes sign from positive to negative as the particle size increases. In other words, the particle is hydrophobic at small size and hydrophilic at large size. This behavior arises from a purely geometrical effect caused by the curvature of the particle-water interface. We explore the consequences of this phenomenon on colloidal stability and find that it dictates the shape of colloidal aggregates.

Modifying the electronic properties of single-walled carbon nanotubes using designed surfactant peptides

The electronic properties of carbon nanotubes can be altered significantly by modifying the nanotube surface. In this study, single-walled carbon nanotubes (SWCNTs) were functionalized noncovalently using designed surfactant peptides, and the resultant SWCNT electronic properties were investigated. These peptides have a common amino acid sequence of X(Valine)(5)(Lysine)(2), where X indicates an aromatic amino acid containing either an electron-donating or electron-withdrawing functional group (i.e. p-amino-phenylalanine or p-cyano-phenylalanine). Circular dichroism spectra showed that the surfactant peptides primarily have random coil structures in an aqueous medium, both alone and in the presence of SWCNTs, simplifying analysis of the peptide/SWCNT interaction. The ability of the surfactant peptides to disperse individual SWCNTs in solution was verified using atomic force microscopy and ultraviolet-visible-near-infrared spectroscopy. The electronic properties of the surfactant peptide/SWCNT composites were examined using the observed nanotube Raman tangential band shifts and the observed additional features near the Fermi level in the scanning tunneling spectroscopy dI/dV spectra. The results revealed that SWCNTs functionalized with surfactant peptides containing electron-donor or electron-acceptor functional groups showed n-doped or p-doped altered electronic properties, respectively. This work unveils a facile and versatile approach to modify the intrinsic electronic properties of SWCNTs using a simple peptide structure, which is easily adaptable to obtain peptide/SWCNT composites for the design of tunable nanoscale electronic devices.

Free energy analysis of vesicle-to-bicelle transformation

A lipid assembly composed of a finite number of lipid molecules can have multiple metastable structures. Using a series of coarse-grained molecular dynamics simulations, we evaluate the free energy profile for the transformation of a small vesicle to a disk-like structure called a bicelle. This free energy is found to be lower than that predicted from continuum elastic theory. For small unilamellar vesicles, the relaxation of the internal structure of the membrane is suggested to play an important role in lowering the free energy barrier for the vesicle-to-bicelle transformation.