Water dynamics around T0 vs R4 of hemoglobin from local hydrophobicity analysis.

The local hydration around tetrameric hemoglobin (Hb) in its T0 and R4 conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the α1ß2 and α2ß1 interfaces, responsible for the quaternary T → R transition, which is encoded in the Monod-Wyman-Changeux model, as well as comparison with earlier computations of the solvent accessible surface area, makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface, whereas "buried surface" reports on the available space for solvent. For simulations with Hb frozen in its T0 and R4 states, the correlation coefficient between LH and buried surface is 0.36 and 0.44, respectively, but it increases considerably if the 95% confidence interval is used. The LH with Hb frozen and flexible changes little for most residues at the interfaces but is significantly altered for a few select ones: Thr41α, Tyr42α, Tyr140α, Trp37ß, Glu101ß (for T0) and Thr38α, Tyr42α, Tyr140α (for R4). The number of water molecules at the interface is found to increase by ∼25% for T0 → R4, which is consistent with earlier measurements. Since hydration is found to be essential to protein function, it is clear that hydration also plays an essential role in allostery.

Genesis of Polyatomic Molecules in Dark Clouds: CO2 Formation on Cold Amorphous Solid Water.

Understanding the formation of molecules under conditions relevant to interstellar chemistry is fundamental to characterize the chemical evolution of the universe. Using reactive molecular dynamics simulations with model-based or high-quality potential energy surfaces provides a means to specifically and quantitatively probe individual reaction channels at a molecular level. The formation of CO2 from collision of CO(1Σ) and O(1D) is characterized on amorphous solid water (ASW) under conditions typical in cold molecular clouds. Recombination takes place on the subnanosecond time scale and internal energy redistribution leads to stabilization of the product with CO2 remaining adsorbed on the ASW on extended time scales. Using a high-level, reproducing kernel-based potential energy surface for CO2, formation into and stabilization of CO2 and COO are observed.

A method for calculating temperature-dependent photodissociation cross sections and rates.

The destruction of molecules by photodissociation plays a major role in many radiation-rich environments, including the evolution of the atmospheres of exoplanets, which often exist close to UV-rich stars. Most current photodissociation calculations and databases assume T = 0 K, which is inadequate for hot exoplanets and stars. A method is developed for computing photodissociation spectra of diatomic molecules as a function of temperature exploiting bound state variational nuclear motion program Duo and post-processing program ExoCross. Discrete transition intensities are spread out to represent a continuous photodissociation spectrum either by Gaussian smoothing or by averaging calculations over a range of different grid sizes. Our approach is tested on four different chemical species (HCl, HF, NaCl and BeH+), showing its ability to reproduce photodissociation cross sections and rates computed with other approaches and experiment. The temperature dependence of photodissociation cross sections and rates is studies showing strong temperature variation of the photodissociation cross sections.

Polarizable Multipolar Molecular Dynamics Using Distributed Point Charges.

Distributed point charge models (DCM) and their minimal variants (MDCM) have been integrated with tools widely used for condensed-phase simulations, including a virial-based barostat and a slow-growth algorithm for thermodynamic integration. Minimal DCM is further developed in a systematic fashion to reduce fitting errors in the electrostatic interaction energy, and a new fragment-based approach offers considerable speedup of the MDCM fitting process for larger molecules with increased numbers of off-centered charged sites. Finally, polarizable (M)DCM is also introduced in the present work. The developments are used in condensed-phase simulations of popular force fields with commonly applied simulation conditions. (M)DCM equivalents for a range of widely used water force fields and for fluorobenzene (PhF) are developed and applied along with the original models to evaluate the impact of reformulating the electrostatic term. Comparisons of the molecular electrostatic potential (MEP), electrostatic interaction energies, and bulk properties from molecular dynamics simulations for a range of models from simple TIPnP (n = 3-5) to the polarizable, multipolar iAMOEBA models for water and an existing quadrupolar model for PhF confirm that DCMs retain the accuracy of the original models, providing a homogeneous, efficient, and generic point charge alternative to a multipolar electrostatic model for force field development and multilevel simulations.

Water Dynamics Around Proteins: T- and R-States of Hemoglobin and Melittin.

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin (Hb) and dimeric melittin. For the T0 to R0 transition in Hb, it is found that LH provides additional molecular-level insight into the Perutz mechanism, i.e., the breaking and formation of salt bridges at the α1/ß2 and α2/ß1 interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 and 120 Å edge length it is observed that following a decrease in LH as a consequence of reduced water density or change of water orientation at the protein/water interface the α/ß interfaces are destabilized; this is a hallmark of the Perutz stereochemical model for the T to R transition in Hb. The present work thus provides a dynamical view of the classical structural model relevant to the molecular foundations of Hb function. For dimeric melittin, earlier results by Cheng and Rossky [ Nature 1998, 392, 696-699] are confirmed and interpreted on the basis of LH from simulations in which the protein structure is frozen. For the flexible melittin dimer, the changes in the local hydration can be as much as 30% greater than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled.

Formation and Stabilization of Ground and Excited-State Singlet O2 upon Recombination of 3P Oxygen on Amorphous Solid Water.

The recombination dynamics of 3P oxygen atoms on cold amorphous solid water to form triplet and singlet molecular oxygen (O2) is investigated under conditions representative of cold clouds. Reactive molecular dynamics simulations including Landau-Zener-based hopping to account for nonadiabatic transitions find that both ground-state (X3Σg-) O2 and molecular oxygen in the two lowest singlet states (a1Δg and b1Σg+) can be formed and the molecular species stabilize through vibrational relaxation. The relative populations of the species are approximately 1:1:1. These results also agree qualitatively with a kinetic model based on simplified wavepacket simulations. The presence and stabilization of higher electronic states of O2 are expected to modify the chemical evolution of cold interstellar (T ∼ 10-50 K) and warmer noctilucent (T ∼ 100 K) clouds.

O2 formation in cold environments.

The diffusional dynamics of atomic oxygen in and on amorphous solid water (ASW) to form molecular oxygen is characterized. Reactive molecular dynamics simulations to study bond breaking and bond formation show that vibrational relaxation of the highly excited diatomic occurs on the 10 ns to 100 ns time scale. The relaxation process is highly nonexponential and can be characterized by a stretched exponential decay reminiscent of the dynamics of glasses. The stretched exponents range from ß = 0.15 for relaxation on the surface to ß = 0.21 for the dynamics in bulk. It is also found that coupling of the O2 relaxation to the internal water modes occurs which speeds up the vibrational relaxation by a factor of 4. Extrapolation of the stretched exponential decay to 1 µs yields a final vibrational quantum number v = 2 for O2(X3Σ-g), consistent with experimental results from photolysis of SO2 on ASW at 193 nm which find v ≤ 3. Desorption energies of water from the surface range from 1.5 to 2.0 kcal mol-1 compared with 1.8 kcal mol-1 found from experiment, depending on whether the water molecules are flexible or not.

Ultra-Fast-VUV Photoemission Study of UV Excited 2-Nitrophenol.

The initial deactivation pathways of gaseous 2-nitrophenol excited at 268 nm were investigated by time-resolved photoelectron spectroscopy (TRPES) with femtosecond-VUV light, produced by a monochromatized high harmonic generation source. TRPES allowed us to obtain new, valuable experimental information about the ultrafast excited-state dynamics of 2-nitrophenol in the gas phase. In accord with recent ab initio on-the-fly nonadiabatic molecular dynamic simulations, our results validate the occurrence of an ultrafast intersystem crossing leading to an intermediate state that decays on a subpicosecond time scale with a branched mechanisms. Two decay pathways are experimentally observed. One probably involves proton transfer, leading to the most stable triplet aci-form of 2-nitrophenol; the second pathway may involve OH rotation. We propose that following intersystem crossing, an ultrafast fragmentation channel leading to OH or HONO loss could also be operative.

Molecular Oxygen Formation in Interstellar Ices Does Not Require Tunneling.

The formation of molecular oxygen in and on amorphous ice in the interstellar medium requires oxygen diffusion to take place. Recent experiments suggest that this process involves quantum tunneling of the oxygen atoms at sufficiently low temperatures. Fitting experimental diffusion rates between 6 and 25 K to an expression that accounts for the roughness of the surface yields excellent agreement. The molecular dynamics of adsorbed oxygen is characterized by rapid intrasite dynamics, followed by intersite transitions over distances of ∼10 Å. Explicit simulations using a realistic free-energy surface for oxygen diffusion on amorphous ice down to 10 K show that quantum tunneling is not required for mobility of adsorbed oxygen. This is confirmed by comparing quantum and classical simulations using the same free-energy surface. The ratio of diffusional and desorption energy Edif/ Edes = 275/1082 ≈ 0.3 is at the lower end of typically used values but is still consistent with the assumptions made in models for interstellar chemistry.

Delays in starting morning operating lists: an analysis of more than 20,000 cases in 22 German hospitals.

INTRODUCTION: Delays in the start of the first operation of the day often lead to conflicts among the involved physicians and nurses. Data on such delays have already been published for individual hospitals, but robust comparative data from a large number of institutions have not been available till now. METHODS: The study is based on the operating room (OR) documentation of four surgical services (general surgery, trauma/orthopedic surgery, gynecology, and ear nose throat [ENT] surgery) in 22 German hospitals over a nine-month period. Three process points ("patient arrival in OR suite," "anesthesia ready," and "incision") were analyzed for the first operation of the day in each OR. RESULTS: 21,357 operations in the first position were analyzed. The percentage of delays differed markedly for the three process points. The incision was delayed in more than 70% of the general surgical and trauma/orthopedic cases, but less often in gynecological (61 ± 24%) and ENT cases (42 ± 29%). The frequency of delays longer than 10 minutes was between 20% and 40%. The mean delay in delayed cases ranged from 14.1 ± 5.4 to 21.6 ± 8.2 minutes depending on the type of service and process point. CONCLUSION: The processes for the first operation of the day are not optimally structured in the hospitals whose cases were analyzed in this study. Delayed starts were common.