OH-Stretching Overtone Induced Dynamics in HSO₃F from Reactive Molecular Dynamics Simulations

The OH-stretch induced dynamics in fluorosulfonic acid (HSO₃F) is characterized from a statistically significant number of trajectories using multisurface adiabatic reactive molecular dynamics (MS-ARMD) simulations. The global reactive potential energy surface, which describes H-transfer and HF-elimination, is parametrized at the MP2/6-311G++(2p,2d) level of theory with an accuracy of better than 1 kcal/mol. Excitation along the OH-local mode leads to H-transfer dynamics but elimination of HF is only observed for excitations with ν ≥ 6 for 1 out of 5000 trajectories. This finding differs fundamentally from the situation for vibrationally induced photodissociation of H₂SO₄ and HSO₃Cl, for which, even with excitations of 4 quanta along the OH-stretch mode, elimination of H₂O and HCl, respectively, is readily observed on the subnanosecond time scale. RRKM rates for HX-elimination in HSO₃X (X = F, Cl) only differ by a factor of 5. The findings from the reactive molecular dynamics simulations together with the RRKM results thus indicate that the origin for a closed HF-production channel is dynamical. This is also consistent with experimental findings for hydrofluoroethanes in shock tubes, which found pronounced non-RRKM behavior

Dynamics of Water/Methanol Mixtures at Functionalized Chromatographic Interfaces

Fully atomistic simulations of water/methanol mixtures of varying compositions (80/20 and 50/50) at chromatographic interfaces with different functionalizations are presented. The dynamical properties in terms of equilibration times and solvent exchange dynamics are characterized and found to depend on the different systems on the nanosecond time scale. The solvent density profile and the structuring of the stationary phase differ for derivatizations including (−CN, NO₂, −NH₂, −C₆H₅) of the C₁₈ chain. The time scale and intensity of the water exchange dynamics differs for the different realizations of the chromatographic systems and ranges from 200 to 500 ps. Water exchange rates depend on solvent composition as well as on the functionalization of alkyl chains. Simulations with acridine as a probe molecule provide atomistic insight into the slot model

Toolkit for the Construction of Reproducing Kernel-Based Representations of Data: Application to Multidimensional Potential Energy Surfaces

In the early days of computation, slow processor speeds limited the amount of data that could be generated and used for scientific purposes. In the age of big data, the limiting factor usually is the method with which large amounts of data are analyzed and useful information is extracted. A typical example from chemistry are high-level ab initio calculations for small systems, which have nowadays become feasible even if energies at many different geometries are required. Molecular dynamics simulations often require several thousand distinct trajectories to be run. Under such circumstances suitable analytical representations of potential energy surfaces (PESs) based on ab initio calculations are required to propagate the dynamics at an acceptable cost. In this work we introduce a toolkit which allows the automatic construction of multidimensional PESs from gridded ab initio data based on reproducing kernel Hilbert space (RKHS) theory. The resulting representations require no tuning of parameters and allow energy and force evaluations at ab initio quality at the same cost as empirical force fields. Although the toolkit is primarily intended for constructing multidimensional potential energy surfaces for molecular systems, it can also be used for general machine learning purposes. The software is published under the MIT license and can be downloaded, modified, and used in other projects for free

Vibrational Spectroscopy and Proton Transfer Dynamics in Protonated Oxalate

The dynamics and infrared spectroscopic signatures of proton transfer in protonated oxalate (<i>p</i>–Oxa) are studied using classical and quantum dynamics. The intermolecular interactions are described by a force field suitable to follow proton transfer. This allows to carry out multiple extended classical molecular dynamics (MD) and ring polymer MD simulations from which the infrared spectrum is determined. Simulations at 600 K sample the quantum mechanical ground state probability distribution and best reproduce the experimentally observed maximum absorption wavelength and part of the line shape. Comparison with the experimentally measured spectrum provides an estimate for the barrier height for proton transfer which can not be determined directly from experiment. A barrier of 4.2 kcal/mol is found to best reproduce the position and width of the infrared absorption of the transferring proton in <i>p</i>–Oxa and also leads to an infrared (IR) spectrum in good agreement with experiment for the deuterated species <i>d</i>–Oxa. A novel means to capture the two resonance forms of oxalate depending on the localization of the excess proton on either CO moiety is found to yield improved results for the spectroscopy in the framework region between 1000 and 2000 cm^–1

Dihedral probability distributions for Phe^E15.

<p>2-dimensional probability distributions <i>p</i>(<i>χ</i>₁, <i>χ</i>₂) of <i>χ</i>₁ and <i>χ</i>₂ dihedral angles upon Xe1a→Xe2 transitions, compared to the equilibrium distribution. A single Phe is reported in the left upper corner, along with the definition of angles <i>χ</i>₁ and <i>χ</i>₂. <i>p</i>(<i>χ</i>₁, <i>χ</i>₂) in panels B and C are different from the equilibrium distribution. Distributions also differ depending on where Xe came from before the transition. Characteristic examples are Xe2→Xe1a→Xe2 vs Xe1b→Xe1a→Xe2 events from panel B and Xe1a→Xe2→Xe1a vs Xe1b→Xe2→Xe1a events from panel C.</p

Leveraging Symmetries of Static Atomic Multipole Electrostatics in Molecular Dynamics Simulations

Multipole (MTP) electrostatics provides the means to describe anisotropic interactions in a rigorous and systematic manner. A number of earlier molecular dynamics (MD) implementations have increasingly relied on the use of molecular symmetry to reduce the (possibly large) number of MTP interactions. Here, we present a CHARMM implementation of MTP electrostatics in terms of spherical harmonics. By relying on a systematic set of reference-axis systems tailored to various chemical environments, we obtain an implementation that is both efficient and scalable for (bio)­molecular systems. We apply the method to a series of halogenated compounds to show (i) energy conservation; (ii) improvements in reproducing thermodynamic properties compared to standard point-charge (PC) models; (iii) performance of the code; and (iv) better stabilization of a brominated ligand in a target protein, compared to a PC force field. The implementation provides interesting perspectives toward a dual PC/MTP resolution, à la QM/MM

Xe position probability distributions, short vs long residence times.

<p>Comparison of probability distributions <i>P</i>(<i>x</i>, <i>y</i>) from many short dwell times (left, 5 ps) with <i>P</i>(<i>x</i>, <i>y</i>) of a simulation with a 1.2 ns dwell time (right) in the Xe1a state. The two distributions differ in shape and size because for short dwell times, Xe samples the available volume with little protein adaptation taking place whereas for long dwell times the protein is able to pack more closely around the Xe atom which typically leads to reduction of the volume of the sampled space.</p

Molecular Dynamics with Conformationally Dependent, Distributed Charges

Accounting for geometry-induced changes in the electronic distribution in molecular simulation is important for capturing effects such as charge flow, charge anisotropy, and polarization. Multipolar force fields have demonstrated their ability to correctly represent chemically significant features such as anisotropy and sigma holes. It has also been shown that off-center point charges offer a compact alternative with similar accuracy. Here, it is demonstrated that allowing relocation of charges within a minimally distributed charge model (MDCM) with respect to their reference atoms is a viable route to capture changes in the molecular charge distribution depending on geometry, i.e., intramolecular polarization. The approach, referred to as “flexible MDCM” (fMDCM), is validated on a number of small molecules and provides accuracies in the electrostatic potential (ESP) of 0.5 kcal/mol on average compared with reference data from electronic structure calculations, whereas MDCM and point charges have root mean squared errors of a factor of 2 to 5 higher. In addition, MD simulations in the NVE ensemble using fMDCM for a box of flexible water molecules with periodic boundary conditions show a width of 0.1 kcal/mol for the fluctuation around the mean at 300 K on the 10 ns time scale. For water, the equilibrium valence angle in the gas phase is found to increase by 2° for simulations in the condensed phase which is consistent with experiment. The accuracy in capturing the geometry dependence of the ESP together with the long-time stability in energy conserving simulations makes fMDCM a promising tool to introduce advanced electrostatics into atomistic simulations

Migration of small ligands in globins: Xe diffusion in truncated hemoglobin N

<div><p>In heme proteins, the efficient transport of ligands such as NO or O₂ to the binding site is achieved via ligand migration networks. A quantitative assessment of ligand diffusion in these networks is thus essential for a better understanding of the function of these proteins. For this, Xe migration in truncated hemoglobin N (trHbN) of <i>Mycobacterium Tuberculosis</i> was studied using molecular dynamics simulations. Transitions between pockets of the migration network and intra-pocket relaxation occur on similar time scales (10 ps and 20 ps), consistent with low free energy barriers (1-2 kcal/mol). Depending on the pocket from where Xe enters a particular transition, the conformation of the side chains lining the transition region differs which highlights the coupling between ligand and protein degrees of freedom. Furthermore, comparison of transition probabilities shows that Xe migration in trHbN is a non-Markovian process. Memory effects arise due to protein rearrangements and coupled dynamics as Xe moves through it.</p></div

Xe1a↔Xe2 transition region.

<p>Xe1a and Xe2 pockets (orange and gray sphere, respectively), together with surrounding residues Val^B6 (cyan), Phe^B9 (green), Phe^E15 (magenta), Gln^E11 (red), and Leu^G12(blue). The minimum energy transition path (in blue cylinder) and one particular transition path (small black spheres) are shown between the two pockets. In grey (background) the ribbon structure of the protein and in licorice the heme-unit.</p