The Low Barrier Hydrogen Bond in the Photoactive Yellow Protein: A Vacuum Artifact Absent in the Crystal and Solution

Journal of the American Chemical Society 138(51), 16620 - 16631 (2016). doi:10.1021/jacs.6b05609

Core hole screening and decay rates of double core ionized first row hydrides.

Because of the high intensity, X-ray free electron lasers allow one to create and probe double core ionized states in molecules. The decay of these multiple core ionized states crucially determines the evolution of radiation damage in single molecule diffractive imaging experiments. Here we have studied the Auger decay in hydrides of first row elements after single and double core ionization by quantum mechanical ab initio calculations. In our approach the continuum wave function of the emitted Auger electron is expanded into spherical harmonics on a radial grid. The obtained decay rates of double K-shell vacancies were found to be systematically larger than those for the respective single …

Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer

In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its…

Force Distribution Analysis of Mechanochemically Reactive Dimethylcyclobutene

Internal molecular forces can guide chemical reactions, yet are not straightforwardly accessible within a quantum mechanical description of the reacting molecules. Here, we present a force-matching force distribution analysis (FM-FDA) to analyze internal forces in molecules. We simulated the ring opening of trans-3,4-dimethylcyclobutene (tDCB) with on-the-fly semiempirical molecular dynamics. The self-consistent density functional tight binding (SCC-DFTB) method accurately described the force-dependent ring-opening kinetics of tDCB, showing quantitative agreement with both experimental and computational data at higher levels. Mechanical force was applied in two different ways, namely, exter…

Anomalous surface diffusion of protons on lipid membranes.

AbstractThe cellular energy machinery depends on the presence and properties of protons at or in the vicinity of lipid membranes. To asses the energetics and mobility of a proton near a membrane, we simulated an excess proton near a solvated DMPC bilayer at 323 K, using a recently developed method to include the Grotthuss proton shuttling mechanism in classical molecular dynamics simulations. We obtained a proton surface affinity of −13.0 ± 0.5 kJ mol−1. The proton interacted strongly with both lipid headgroup and linker carbonyl oxygens. Furthermore, the surface diffusion of the proton was anomalous, with a subdiffusive regime over the first few nanoseconds, followed by a superdiffusive re…

Cationic and Anionic Impact on the Electronic Structure of Liquid Water

Hydration shells around ions are crucial for many fundamental biological and chemical processes. Their local physicochemical properties are quite different from those of bulk water and hard to probe experimentally. We address this problem by combining soft X-ray spectroscopy using a liquid jet and molecular dynamics (MD) simulations together with ab initio electronic structure calculations to elucidate the water–ion interaction in a MgCl2 solution at the molecular level. Our results reveal that salt ions mainly affect the electronic properties of water molecules in close vicinity and that the oxygen K-edge X-ray emission spectrum of water molecules in the first solvation shell differs signi…

Correction to "Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides".

Quantifying Artifacts in Ewald Simulations of Inhomogeneous Systems with a Net Charge

Ewald summation, which has become the de facto standard for computing electrostatic interactions in biomolecular simulations, formally requires that the simulation box is neutral. For non-neutral systems the Ewald algorithm implicitly introduces a uniform background charge distribution that e ectively neutralizes the simulation box. Because a uniform distribution of counter charges typically deviates from the spatial distribution of counterions in real systems, artifacts may arise, in particular in systems with an inhomogeneous dielectric constant. Here we derive an analytical expression for the e ect of using an implicit background charge instead of explicit counterions, on the chemical po…

GROMEX: A Scalable and Versatile Fast Multipole Method for Biomolecular Simulation

Atomistic simulations of large biomolecular systems with chemical variability such as constant pH dynamic protonation offer multiple challenges in high performance computing. One of them is the correct treatment of the involved electrostatics in an efficient and highly scalable way. Here we review and assess two of the main building blocks that will permit such simulations: (1) An electrostatics library based on the Fast Multipole Method (FMM) that treats local alternative charge distributions with minimal overhead, and (2) A $λ$-dynamics module working in tandem with the FMM that enables various types of chemical transitions during the simulation. Our $λ$-dynamics and FMM implementations d…