The influence of water potential in simulation: a catabolite activator protein case study.

We present a rare comparison of structures of the same protein but generated by different potentials. We used four popular water potentials (SPC, TIP3P, TIP4P, TIP5P) in conjunction with the equally popular ff99SB. However, the ff12SB protein potential was used with TI3P only. Simulations (60 ns) were run on the catabolite activator protein (CAP), which is a textbook case of allosteric interaction. Overall, all potentials generated largely similar structures but failed to reproduce a crucial structural feature determined by NMR experiment. This example shows the need to develop next-generation potentials. Graphical abstract Catabolite activator protein.

The hydration of serine: multipole moments versus point charges.

Next-generation force fields must incorporate improved electrostatic potentials in order to increase the reliability of their predictions. A crucial decision toward this goal is to abandon point charges in favour of multipole moments centered on nuclear sites. Here we compare the geometries generated by quantum topological multipole moments with those generated by four popular point charge models (TAFF, OPLS-AA, MMFF94x and PFROSST) for a hydrated serine. A main feature of this study is the dual comparison made, both at static level (geometry optimisation via energy minimisation) and at dynamic level (via molecular dynamics and radial/spatial distribution function analysis). At static level, multipolar electrostatics best reproduces the ab initio reference geometry. At dynamic level, multipolar electrostatics produces more structure than point charge electrostatics does, over the whole range. From our previous work on liquid water [Int. J. Quantum. Chem., 2004, 99, 685], where agreement with experiment only occurs when using multipole moments, we deduce that our predictions for hydrated serine will also be closer to experiment when using multipolar electrostatics. The spatial distribution function shows that only multipolar electrostatics shows pronounced structure at long range. Even at short range there are many regions where waters appear in the system governed by multipolar electrostatics but not in that governed by point charges.

Aqueous imidazole solutions: a structural perspective from simulations with high-rank electrostatic multipole moments.

Imidazole is a small but important molecule occurring as a structure fragment in systems from amino acids, over ionic liquids, to synthetic polymers. Here we focus on the structure and dynamics of imidazole in water at ambient conditions, using both radial and spatial distribution functions. Molecular dynamics simulations were carried out for various imidazole concentrations, using a traditional point-charge potential and a high-rank multipolar potential. The difference in the description of the electrostatics leads to sizable quantitative differences (e.g., the diffusion coefficient) but also qualitative differences in the local structure. In contrast to a point-charge potential, the multipolar potential favors hydrogen-bonded chainlike imidazole dimers over stacked dimers.

Simulation of liquid imidazole using a high-rank quantum topological electrostatic potential.

Rigid body molecular dynamics simulations were carried out on pure liquid imidazole at four different temperatures and at 1 atm. Imidazole, which is important both in life science and materials science, is one of the simplest molecules to possess both a lone pair and a π system. These two features are known to benefit from multipolar electrostatics. Here the electrostatic interaction is governed by atomic multipole moments obtained from topologically partitioned ab initio electron densities. The non-electrostatic terms are modeled with Lennard-Jones parameters adjusted to fit the experimental liquid density. All σ values are incrementally increased by one single scaling factor. We report on how the presence of multipolar electrostatics influences the local structure, dynamics and thermodynamics of the liquid compared to electrostatics by atomic point charges. The point charge force field exaggerates the number of π-stacked dimers in the liquid, and underestimates the number of hydrogen-bonded dimers. The effect of the temperature on the local structure of liquid imidazole was analysed using radial and spatial distribution functions.

An investigation of the conductivity of peptide nanotube networks prepared by enzyme-triggered self-assembly.

We demonstrate that nanotubular networks formed by enzyme-triggered self-assembly of Fmoc-L3 (9-fluorenylmethoxycarbonyl-tri-leucine) show significant charge transport. FT-IR, fluorescence spectroscopy and wide angle X-ray scattering (WAXS) data confirm formation of beta-sheets that are locked together viapi-stacking interactions. Molecular dynamics simulations confirmed the pi-pi stacking distance between fluorenyl groups to be 3.6-3.8 A. Impedance spectroscopy demonstrated that the nanotubular xerogel networks possess minimum sheet resistances of 0.1 MOmega/sq in air and 500 MOmega/sq in vacuum (pressure: 1.03 mbar) at room temperature, with the conductivity scaling linearly with the mass of peptide in the network. These materials may provide a platform to interface biological components with electronics.

Properties of liquid water from a systematic refinement of a high-rank multipolar electrostatic potential.

We build on previous work [S. Y. Liem and P. L. A. Popelier, J. Chem. Theory Comput. 4, 353 (2008)], where for the first time, a high-rank multipolar electrostatic potential was used in molecular dynamics simulations of liquid water at a wide range of pressures and temperatures, and using a multipolar Ewald summation. Water is represented as a rigid body, with atomic multipole moments defined by quantum chemical topology partitioning its gas phase electron density. The effect of the level of theory on the local structure of liquid water is systematically addressed. Values for Lennard-Jones (LJ) parameters are optimized, for both oxygen and hydrogen atoms, against bulk properties. The best LJ parameters were then used in a set of simulations at 30 different temperatures (1 atm) and another set at 11 different pressures (at 298 K). Inclusion of the hydrogen LJ parameters significantly increases the self-diffusion coefficient. The behavior of bulk properties was studied and the local water structure analyzed by both radial and spatial distribution functions. Comparisons with familiar point-charge potentials, such as TIP3P, TIP4P, TIP5P, and simple point charge, show the benefits of multipole moments.

Room temperature ionic liquids containing low water concentrations-a molecular dynamics study.

We have performed classical molecular dynamics to study the properties of a water-miscible and a water-immiscible room-temperature ionic liquid when mixed with small quantities of water. The two ionic liquids consist of the same 1-ethyl-3-methylimidazolium ([EMIM]) cation combined with either the boron tetrafluoride ([BF(4)]) or bis(trifluoromethylsulfonyl)imide ([NTf(2)]) anion. It is found that, in both ionic liquids, water clusters of varying sizes are typically hydrogen bonded to two anions with the cation playing a minor role. We also highlight the difficulties of obtaining dynamic quantities such as self-diffusion coefficients from simulations of such viscous systems.

Properties and 3D Structure of Liquid Water: A Perspective from a High-Rank Multipolar Electrostatic Potential.

We propose a new rigid, nonpolarizable high-rank multipolar potential for the simulation of liquid water. The electrostatic interaction is represented by spherical tensor multipole moments on oxygen and hydrogen, up to hexadecupole. The Quantum Chemical Topology (QCT) method yields the atomic multipole moments from a MP2/aug-cc-p-VTZ electron density of a single water molecule in the gas phase. These moments reproduce the experimental molecular dipole and quadrupole moment within less than 1%. Given its high-rank multipole moments, used in conjunction with a consistent high-rank multipolar Ewald summation, the QCT potential is ideal to assess the performance of exhaustive "gas phase" electrostatics in molecular dynamics simulations of liquids. The current article explores the performance of this potential at 17 temperatures between -35 °C (238 K) and 90 °C (363 K) and at 7 pressures between 1 and 10 000 atm. The well-known maximum in the liquid's density at 4 °C is reproduced at 6 °C. Six bulk properties are calculated and found to deviate from experiment in a homogeneous manner, that is, without serious outliers, compared to several other potentials. Spatial distribution functions (i.e., gOO(r,Ω)) and the (more common) radial distribution functions are used to analyze the local water structure. At the lone pair side of a central water, neighboring waters form a continuous horseshoe-like distribution, with substantial narrowing in the central part. The latter feature is unique to the QCT potential. Under high pressure, the local structure undergoes dramatic rearrangement and results in the collapse of second shell neighbors into the interstitial region of the first shell, which is in close agreement with experiment. Our results also corroborate the suggestion that the local hydrogen-bonded network remains largely intact even under such conditions.