Hybrid particle‐field molecular dynamics simulations: Parallelization and benchmarks

The parallel implementation of a recently developed hybrid scheme for molecular dynamics (MD) simulations (Milano and Kawakatsu, J Chem Phys 2009, 130, 214106) where self‐consistent field theory (SCF) and particle models are combined is described. Because of the peculiar formulation of the hybrid method, considering single particles interacting with density fields, the most computationally expensive part of the hybrid particle‐field MD simulation can be efficiently parallelized using a straightforward particle decomposition algorithm. Benchmarks of simulations, including comparisons of serial MD and MD‐SCF program profiles, serial MD‐SCF and parallel MD‐SCF program profiles, and parallel benchmarks compared with efficient MD program GROMACS 4.5.4 are tested and reported. The results of benchmarks indicate that the proposed parallelization scheme is very efficient and opens the way to molecular simulations of large scale systems with reasonable computational costs. © 2012 Wiley Periodicals, Inc.     

Molecular dynamics simulations of aqueous ions at the liquid–vapor interface accelerated using graphics processors

Molecular dynamics (MD) simulations are a vital tool in chemical research, as they are able to provide an atomistic view of chemical systems and processes that is not obtainable through experiment. However, large‐scale MD simulations require access to multicore clusters or supercomputers that are not always available to all researchers. Recently, scientists have returned to exploring the power of graphics processing units (GPUs) for various applications, such as MD, enabled by the recent advances in hardware and integrated programming interfaces such as NVIDIA's CUDA platform. One area of particular interest within the context of chemical applications is that of aqueous interfaces, the salt solutions of which have found application as model systems for studying atmospheric process as well as physical behaviors such as the Hoffmeister effect. Here, we present results of GPU‐accelerated simulations of the liquid–vapor interface of aqueous sodium iodide solutions. Analysis of various properties, such as density and surface tension, demonstrates that our model is consistent with previous studies of similar systems. In particular, we find that the current combination of water and ion force fields coupled with the ability to simulate surfaces of differing area enabled by GPU hardware is able to reproduce the experimental trend of increasing salt solution surface tension relative to pure water. In terms of performance, our GPU implementation performs equivalent to CHARMM running on 21 CPUs. Finally, we address possible issues with the accuracy of MD simulaions caused by nonstandard single‐precision arithmetic implemented on current GPUs. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

Controlling Aqueous Self‐Assembly Mechanisms by Hydrophobic Interactions

We report an innovative template‐assisted synthetic protocol for the selective functionalization of terminal triple bonds in oligophenyleneethynylenes (OPE) by pre‐organization in aqueous solution. By this approach, three new OPE‐based bolaamphiphiles substituted with hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOx) chains of different length have been synthesized. The chain length was observed to strongly influence the aqueous supramolecular polymerization: bolaamphiphiles with longer hydrophilic chains aggregate into spherical nanoparticles in a stepwise fashion, whereas 2D anisotropic platelets are formed cooperatively if shorter PEtOx chains are used. Our results demonstrate that hydrophobic interactions can be strong enough to trigger cooperative effects in aqueous self‐assembly processes.     

CENCALC: A computational tool for conformational entropy calculations from molecular simulations

We present the CENCALC software that has been designed to estimate the conformational entropy of single molecules from extended Molecular Dynamics (MD) simulations in the gas‐phase or in solution. CENCALC uses both trajectory coordinates and topology information in order to characterize the conformational states of the molecule of interest by discretizing the time evolution of internal rotations. The implemented entropy methods are based on the mutual information expansion, which is built upon the converged probability density functions of the individual torsion angles, pairs of torsions, triads, and so on. Particularly, the correlation‐corrected multibody local approximation selects an optimum cutoff in order to retrieve the maximum amount of genuine correlation from a given MD trajectory. We illustrate these capabilities by carrying out conformational entropy calculations for a decapeptide molecule either in its unbound form or in complex with a metalloprotease enzyme. CENCALC is distributed under the GNU public license at http://sourceforge.net/projects/cencalc/ .     

Implicit and explicit solvent models for modeling a bifunctional arene ruthenium hydrogen‐storage catalyst: A classical and ab initio molecular simulation study

Classical and ab initio, density functional theory‐ and semiempirical‐based molecular simulation, including molecular dynamics, have been carried out to compare and contrast the effect of explicit and implicit solvation representation of tetrahydrofuran (THF) solvent on the structural, energetic, and dynamical properties of a novel bifunctional arene ruthenium catalyst embedded therein. Particular scrutiny was afforded to hydrogen‐bonding and energetic interactions with the THF liquid. It was found that the presence of explicit THF solvent molecules is required to capture an accurate picture of the catalyst's structural properties, particularly in view of the importance of hydrogen bonding with the surrounding THF molecules. This has implications for accurate modeling of the reactivity of the catalyst. © 2014 Wiley Periodicals, Inc.     

GENESIS 1.1: A hybrid‐parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms

GENeralized‐Ensemble SImulation System (GENESIS) is a software package for molecular dynamics (MD) simulation of biological systems. It is designed to extend limitations in system size and accessible time scale by adopting highly parallelized schemes and enhanced conformational sampling algorithms. In this new version, GENESIS 1.1, new functions and advanced algorithms have been added. The all‐atom and coarse‐grained potential energy functions used in AMBER and GROMACS packages now become available in addition to CHARMM energy functions. The performance of MD simulations has been greatly improved by further optimization, multiple time‐step integration, and hybrid (CPU + GPU) computing. The string method and replica‐exchange umbrella sampling with flexible collective variable choice are used for finding the minimum free‐energy pathway and obtaining free‐energy profiles for conformational changes of a macromolecule. These new features increase the usefulness and power of GENESIS for modeling and simulation in biological research. © 2017 Wiley Periodicals, Inc.     

Electrohydrodynamics of spherical polyampholyte‐grafted nanoparticles: Multiscale simulations by coupling of molecular dynamics and lattice‐boltzmann method

We perform multiscale simulations based on the coupling of molecular dynamics and lattice‐Boltzmann (LB) method to study the electrohydrodynamics of a polyampholyte‐grafted spherical nanoparticle. The long‐range hydrodynamic interactions are modeled by coupling the movement of particles to a LB fluid. Our results indicate that the net‐neutral soft particle moves with a nonzero mobility under applied electric fields. We systematically explore the effects of different parameters, including the chain length, grafting density, electric field, and charge sequence, on the structures of the polymer layer and the electrophoretic mobility of the soft particle. It shows that the mobility of nanoparticles has remarkable dependence on these parameters. We find that the deformation of the polyampholyte chains and the ion distribution play dominant roles in modulating the electrokinetic behavior of the polyampholyte‐grafted particle. The enhancement or reduction in the accumulation of counterions around monomers can be attributed to the polymer layer structure and the conformational transition of the chains in the electric field. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1435–1447     

Dynamics and structural changes of small water clusters on ionization

Despite utmost importance in understanding water ionization process, reliable theoretical results of structural changes and molecular dynamics (MD) of water clusters on ionization have hardly been reported yet. Here, we investigate the water cations [(H₂O)_{n = 2–6}⁺] with density functional theory (DFT), Möller–Plesset second‐order perturbation theory (MP2), and coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. The complete basis set limits of interaction energies at the CCSD(T) level are reported, and the geometrical structures, electronic properties, and infrared spectra are investigated. The characteristics of structures and spectra of the water cluster cations reflect the formation of the hydronium cation moiety (H₃O⁺) and the hydroxyl radical. Although most density functionals fail to predict reasonable energetics of the water cations, some functionals are found to be reliable, in reasonable agreement with high‐level ab initio results. To understand the ionization process of water clusters, DFT‐ and MP2‐based Born‐Oppenheimer MD (BOMD) simulations are performed on ionization. On ionization, the water clusters tend to have an Eigen‐like form with the hydronium cation instead of a Zundel‐like form, based on reliable BOMD simulations. For the vertically ionized water hexamer, the relatively stable (H₂O)₅⁺ (5sL4A) cluster tends to form with a detached water molecule (H₂O). © 2013 Wiley Periodicals, Inc.     

DNA–Polymer Nanostructures by RAFT Polymerization and Polymerization‐Induced Self‐Assembly

Nanostructures derived from amphiphilic DNA–polymer conjugates have emerged prominently due to their rich self‐assembly behavior; however, their synthesis is traditionally challenging. Here, we report a novel platform technology towards DNA–polymer nanostructures of various shapes by leveraging polymerization‐induced self‐assembly (PISA) for polymerization from single‐stranded DNA (ssDNA). A “grafting from” protocol for thermal RAFT polymerization from ssDNA under ambient conditions was developed and utilized for the synthesis of functional DNA–polymer conjugates and DNA–diblock conjugates derived from acrylates and acrylamides. Using this method, PISA was applied to manufacture isotropic and anisotropic DNA–polymer nanostructures by varying the chain length of the polymer block. The resulting nanostructures were further functionalized by hybridization with a dye‐labelled complementary ssDNA, thus establishing PISA as a powerful route towards intrinsically functional DNA–polymer nanostructures.     

Self‐Assembly of Bare/Polymer‐Grafted Nanoparticle Blends in Homopolymer

The self‐assembly of a binary blend of nanoparticles in a homopolymer matrix using molecular dynamics (MD) simulations is studied here. The systems consist of polymer matrix, “bare” ungrafted spherical nanoparticles and polymer‐grafted nanoparticles, where the particle cores are identical and grafted chains are similar to matrix polymer. It is observed that addition of grafted nanoparticles to a blend of polymer and bare particles can result in the formation of anisotropic structures. By carefully selecting the graft density and molecular weight of the grafted chains, the clusters go from spherical to cylindrical to branched cylinders. This study suggests that it is indeed possible to control the morphology of bare nanoparticles in polymer without directly modifying their surface properties. It is believed that this phenomenon might be of high importance, especially in cases such as polymer‐based solar cells, where it is not feasible to graft the nanoparticles with polymer chains to achieve a greater level of control over the morphology.

     

Entropically Driven Self‐Assembly of Bolaamphiphilic Perylene Dyes in Water

The specific hydrophobic effect involved in the self‐assembly of a bolaamphiphilic perylene bisimide (PBI) dye bearing oligoethylene glycol (OEG) chains has been identified. In pure water, the self‐assembly is entropically driven and enthalpically disfavored, as explored by optical spectroscopy and isothermal titration calorimetry studies. Besides strong π–π interactions between the PBI units that are primarily of enthalpic nature, the major contribution to the self‐assembly is the gain of entropy by release of confined water molecules from the hydration shell of the hydrophilic OEG moieties. Both contributions favor self‐assembly, but their countervailing thermodynamic parameters are reflected in an uncommon temperature dependence, which can be inverted upon gradual addition of an organic cosolvent that makes the π–π interaction increasingly dominant.     

Enabling grand‐canonical Monte Carlo: Extending the flexibility of GROMACS through the GromPy python interface module

We report on a python interface to the GROMACS molecular simulation package, GromPy (available at https://github.com/GromPy ). This application programming interface (API) uses the ctypes python module that allows function calls to shared libraries, for example, written in C. To the best of our knowledge, this is the first reported interface to the GROMACS library that uses direct library calls. GromPy can be used for extending the current GROMACS simulation and analysis modes. In this work, we demonstrate that the interface enables hybrid Monte‐Carlo/molecular dynamics (MD) simulations in the grand‐canonical ensemble, a simulation mode that is currently not implemented in GROMACS. For this application, the interplay between GromPy and GROMACS requires only minor modifications of the GROMACS source code, not affecting the operation, efficiency, and performance of the GROMACS applications. We validate the grand‐canonical application against MD in the canonical ensemble by comparison of equations of state. The results of the grand‐canonical simulations are in complete agreement with MD in the canonical ensemble. The python overhead of the grand‐canonical scheme is only minimal. © 2012 Wiley Periodicals, Inc.     

Interplay between H‐Bonding and Preorganization in the Evolution of Self‐Assembled Systems

Cooperative π–π interactions and H‐bonding are frequently exploited in supramolecular polymerization; however, close scrutiny of their mutual interplay has been largely unexplored. Herein, we compare the self‐assembly behavior of a series of C₂‐ and C₃‐symmetrical oligophenyleneethynylenes differing in their amide topology (N‐ or C‐centered). This subtle structural modification brings about drastic changes in their photophysical and supramolecular properties, highlighting the reciprocal impact of H‐bonding vs. preorganization on the evolution and final outcome of supramolecular systems.     

Rapid parameterization of small molecules using the force field toolkit

The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions of common classical force fields, for example, General Amber Force Field and CHARMM General Force Field, have posited guidelines for parameterization of small molecules, many technical challenges remain that have hampered their wide‐scale extension. The Force Field Toolkit (ffTK), described herein, minimizes common barriers to ligand parameterization through algorithm and method development, automation of tedious and error‐prone tasks, and graphical user interface design. Distributed as a VMD plugin, ffTK facilitates the traversal of a clear and organized workflow resulting in a complete set of CHARMM‐compatible parameters. A variety of tools are provided to generate quantum mechanical target data, setup multidimensional optimization routines, and analyze parameter performance. Parameters developed for a small test set of molecules using ffTK were comparable to existing CGenFF parameters in their ability to reproduce experimentally measured values for pure‐solvent properties (<15% error from experiment) and free energy of solvation (±0.5 kcal/mol from experiment). © 2013 Wiley Periodicals, Inc.     

Single‐Chain Magnetic Behavior in a Hetero‐Tri‐Spin Complex Mediated by Supramolecular Interactions with TCNQF.− Radicals

The self‐assembly of organic TCNQF^.? radicals (2‐fluoro‐7,7,8,8‐tetracyano‐p‐quinodimethane) and the anisotropic [Tb(valpn)Cu]³⁺ dinuclear cations produced a single‐chain magnet (SCM) involving stacking interactions of TCNQF^.? radicals (H₂valpn is the Schiff base from the condensation of o‐vanillin with 1,3‐diaminopropane). Static and dynamic magnetic characterizations reveal that the effective energy barrier for the reversal of the magnetization in this hetero‐tri‐spin SCM is significantly larger than the barrier of the isolated single‐molecule magnet based on the {TbCu} dinuclear core.     

A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly

The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well.     

A Double Cation–π‐Driven Strategy Enabling Two‐Dimensional Supramolecular Polymers as Efficient Catalyst Carriers

The cation–π interaction is a strong non‐covalent interaction that can be used to prepare high‐strength, stable supramolecular materials. However, because the molecular plane of a cation‐containing group and that of aromatic structure are usually perpendicular when forming a cation–π complex, it is difficult to exploit the cation–π interaction to prepare a 2D self‐assembly in which the molecular plane of all the building blocks are parallel. Herein, a double cation–π‐driven strategy is proposed to overcome this difficulty and have prepared 2D self‐assemblies with long‐range ordered molecular hollow hexagons. The double cation–π interaction makes the 2D self‐assemblies stable. The 2D self‐assemblies are to be an effective carrier that can eliminate metal‐nanoparticle aggregation. Such 2D assembly/palladium nanoparticle hybrids are shown to exhibit recyclability and superior catalytic activity for a model reaction.     

Effect of Head‐Group Chemistry on Surface‐Mediated Molecular Self‐Assembly

Surface molecular self‐assembly is a fast advancing field with broad applications in sensing, patterning, device assembly, and biochemical applications. A vast number of practical systems utilize alkane thiols supported on gold surfaces. Whereas a strong Au? S bond facilitates robust self‐assembly, the interaction is so strong that the surface is reconstructed, leaving etch pits that render the monolayers susceptible to degradation. By using different head group elements to adcust the molecule–surface interaction, a vast array of new systems with novel properties may be formed. In this paper we use a carefully chosen set of molecules to make a direct comparison of the self‐assembly of thioether, selenoether, and phosphine species on Au(111). Using the herringbone reconstruction of gold as a sensitive readout of molecule–surface interaction strength, we correlate head‐group chemistry with monolayer (ML) properties. It is demonstrated that the hard/soft rules of inorganic chemistry can be used to rationalize the observed trend of molecular interaction strengths with the soft gold surface, that is, P>Se>S. We find that the structure of the monolayers can be explained by the geometry of the molecules in terms of dipolar, quadrupolar, or van der Waals interactions between neighboring species driving the assembly of distinct ordered arrays. As this study directly compares one element with another in simple systems, it may serve as a guide for the design of self‐assembled monolayers with novel structures and properties.     

A combined semiempirical and DFT computational protocol for studying bioorganometallic complexes: Application to molybdocene–cysteine complexes

Computational methods can help in the design of new bioorganometallic compounds. However, the presence of multihapto or σ/π metal‐ligand bonding still precludes the direct application of either pure molecular mechanics (MM) or hybrid quantum mechanics‐MM methods to study the flexibility of biomolecules in complex with organometallics. Herein, we present a computational protocol aimed to the evaluation of the relative free energies of bioorganometallic compounds, which explores the conformational space by means of Molecular Dynamics simulations using the semiempirical PM6 method coupled with the COnductor‐like Screening MOdel solvation model followed by density functional theory (DFT) calculations including the DFT‐D3 dispersion energy correction on the most stable conformers. This protocol is applied to investigate the complexes formed between cysteine and the molybdocene entity Cp₂Mo²⁺ (Cp?η⁵? C₅H₅), which has received considerable attention due to its potential antitumor activity and chemical reactivity. The calculated structures and free energies are in agreement with those of the experimentally detected molybdocene‐cysteine adducts and allow us to investigate the reaction mechanism for the formation of the most stable 1:1 and 1:2 adducts. © 2013 Wiley Periodicals, Inc.     

Anisotropic Self‐Assembly of Citrate‐Coated Gold Nanoparticles on Fluidic Liposomes

The behavior of self‐assembly processes of nanoscale particles on plasma membranes can reveal mechanisms of important biofunctions and/or intractable diseases. Self‐assembly of citrate‐coated gold nanoparticles (cAuNPs) on liposomes was investigated. The adsorbed cAuNPs were initially fixed on the liposome surfaces and did not self‐assemble below the phospholipid phase transition temperature (T_m). In contrast, anisotropic cAuNP self‐assembly was observed upon heating of the composite above the T_m, where the phospholipids became fluid. The number of self‐assembled NPs is conveniently controlled by the initial mixing ratio of cAuNPs and liposomes. Gold nanoparticle protecting agents strongly affected the self‐assembly process on the fluidic membrane.