Toshifumi Mori

Role of Rydberg states in the photochemical dynamics of ethylene.

We use the ab initio multiple spawning method with potential energy surfaces and nonadiabatic coupling vectors computed from multistate multireference perturbation theory (MSPT2) to follow the dynamics of ethylene after photoexcitation. We introduce an analytic formulation for the nonadiabatic coupling vector in the context of MSPT2 calculations. We explicitly include the low-lying 3s Rydberg state which has been neglected in previous ab initio molecular dynamics studies of this process. We find that although the 3s Rydberg state lies below the optically bright ππ* state, little population gets trapped on this state. Instead, the 3s Rydberg state is largely a spectator in the photodynamics, with little effect on the quenching mechanism or excited state lifetime. We predict the time-resolved photoelectron spectrum for ethylene and point out the signature of Rydberg state involvement that should be easily observed.

Molecular simulation of water and hydration effects in different environments: challenges and developments for DFTB based models.

We discuss the description of water and hydration effects that employs an approximate density functional theory, DFTB3, in either a full QM or QM/MM framework. The goal is to explore, with the current formulation of DFTB3, the performance of this method for treating water in different chemical environments, the magnitude and nature of changes required to improve its performance, and factors that dictate its applicability to reactions in the condensed phase in a QM/MM framework. A relatively minor change (on the scale of kBT) in the O–H repulsive potential is observed to substantially improve the structural properties of bulk water under ambient conditions; modest improvements are also seen in dynamic properties of bulk water. This simple change also improves the description of protonated water clusters, a solvated proton, and to a more limited degree, a solvated hydroxide. By comparing results from DFTB3 models that differ in the description of water, we confirm that proton transfer energetics are adequately described by the standard DFTB3/3OB model for meaningful mechanistic analyses. For QM/MM applications, a robust parametrization of QM-MM interactions requires an explicit consideration of condensed phase properties, for which an efficient sampling technique was developed recently and is reviewed here. The discussions help make clear the value and limitations of DFTB3 based simulations, as well as the developments needed to further improve the accuracy and transferability of the methodology.

Atomic-scale origins of slowness in the cyanobacterial circadian clock

Biochemical basis of a 24-hour clock Circadian clocks keep organisms in synch with such daily cycles as illumination, activity, and food availability. The circadian clock in cyanobacteria has the necessary 24-hour period despite its three component proteins having biochemical activities that occur on a much faster time scale. Abe et al. focused on the cyanobacterial clock component KaiC, an adenosine triphosphatase (ATPase) that can autophosphorylate and autodephosphorylate. The slow ATPase activity of KaiC, which is linked to a peptide isomerisation, provided the slow kinetics that set the speed of the 24-hour clock. Chang et al. found that another clock component, KaiB, also has slow changes in its protein conformation that help to set the oscillation period of the clock and its signaling output. Science, this issue pp. 312 and 324 A slow adenosine triphosphatase reaction sets the pace of a circadian clock. Circadian clocks generate slow and ordered cellular dynamics but consist of fast-moving bio-macromolecules; consequently, the origins of the overall slowness remain unclear. We identified the adenosine triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock. Crystal structures of the ATPase revealed that the slowness of this ATPase arises from sequestration of a lytic water molecule in an unfavorable position and coupling of ATP hydrolysis to a peptide isomerization with high activation energy. The slow ATPase is coupled with another ATPase catalyzing autodephosphorylation in the carboxyl-terminal half of KaiC, yielding the circadian response frequency of intermolecular interactions with other clock-related proteins that influences the transcription and translation cycle.

An Explicit Consideration of Desolvation is Critical to Binding Free Energy Calculations of Charged Molecules at Ionic Surfaces.

Identifying factors that control the strength and specificity of interactions between peptides and nanoparticles is essential for understanding the potential beneficial and deleterious effects of nanoparticles on biological systems. Computer simulations are valuable in this context, although the reliability of such calculations depends on the force field and sampling algorithm, as well as how the binding constant and binding free energy are defined; the latter must be carefully defined with a clear connection to microscopic models based on statistical mechanics. Using the example of formate binding to the rutile titanium dioxide (TiO2) (110) surface, we demonstrate that a reliable description of the binding process requires an explicit consideration of changes in the solvation state of the binding site. Specifically, we carry out metadynamics simulations in which the solvent coordination number of the binding site, s, is introduced as a collective variable in addition to the vertical distance of the adsorbate to the surface (z). The resulting two-dimensional potential of mean force (2D-PMF) clearly shows that explicitly including the local desolvation of the binding site on the TiO2 surface strongly impacts the convergence and result of the binding free energy calculations. Projecting the 2D-PMF into a one-dimensional PMF along either z or s leads to large errors in the free energy barriers. Results from metadynamics simulations are quantitatively supported by independent alchemical free energy simulations, in which the solvation state of the binding site is also carefully considered by explicitly introducing water molecules to the binding site as the adsorbate is decoupled from the system. On the other hand, preliminary committor analysis for the approximate transition state ensemble constructed based on the 2D-PMF suggests that to properly describe the binding/unbinding kinetics, variables beyond s and z, such as those describing the hydrogen bonding pattern of the adsorbate and surface water, need to be included. We expect that the insights and computational methodologies established in this work will be generally applicable to the analysis of binding interactions between highly charged adsorbates and ionic surfaces in solution, such as those implicated in peptide/nanoparticle binding and biomineralization processes.

Grignard Reagents in Solution: Theoretical Study of the Equilibria and the Reaction with a Carbonyl Compound in Diethyl Ether Solvent

The equilibria of Grignard reagents, CH3MgCl and CH3MgBr, in diethyl ether (Et2O) solvent as well as the reaction of the reagents with acetone are studied theoretically. To describe the equilibria and reactions in Et2O solvent, we employ the reference interaction site model self-consistent field method with the second-order Møller-Plesset perturbation (RISM-MP2) free energy gradient method. Since the solvent molecules strongly coordinate to the Grignard reagents, we construct a cluster model by including several Et2O molecules into the quantum mechanical region and embed it into the bulk solvent. We propose that, instead of the traditionally accepted cyclic dimer, the linear form of dimer is as stable as the monomer pair and participates in the equilibria. For the reaction with acetone, two important reaction paths (i.e., monomeric and linear dimeric paths) are studied. It is found that the barrier height for the monomeric path is much higher than that for the linear dimeric path, indicating that the reaction of the Grignard reagent with acetone proceeds through the linear dimeric reaction path. The change of solvation structure during the reaction is examined. On the basis of the calculated free energy profiles, the entire reaction mechanisms of the Grignard reagents with aliphatic ketones in Et2O solvent are discussed.

Photochemical Dynamics of Ethylene Cation C2H4

We present a theoretical study of the nonadiabatic effects in ethylene cation C2H4(+), the simplest π radical cation, after photoexcitation to its three lowest doublet excited states. Two families of conical intersections are found, with minimum energy structures characterized by planar and twisted geometries. Ab initio multiple spawning dynamical calculations suggest that the competition between these relaxation pathways depends strongly on the initial excited state, with excited state lifetimes in the 30-60 fs range. Ultrafast decay via planar geometries deposits the molecule near a bridged minimum on the ground state, allowing prompt H migration events. The alternative pathway mediated by torsional motion induces important backspawned population transfer promoted by hindered rotations. The results allow us to revisit earlier vibrationally-mediated photodissociation experiments and shed light on the electronic relaxation dynamics of a prototypical radical cation subject to strong vibronic interactions.

Dynamic heterogeneity in the folding/unfolding transitions of FiP35

Molecular dynamics simulations have become an important tool in studying protein dynamics over the last few decades. Atomistic simulations on the order of micro- to milliseconds are becoming feasible and are used to study the state-of-the-art experiments in atomistic detail. Yet, analyzing the high-dimensional-long-temporal trajectory data is still a challenging task and sometimes leads to contradictory results depending on the analyses. To reveal the dynamic aspect of the trajectory, here we propose a simple approach which uses a time correlation function matrix and apply to the folding/unfolding trajectory of FiP35 WW domain [Shaw et al., Science 330, 341 (2010)]. The approach successfully characterizes the slowest mode corresponding to the folding/unfolding transitions and determines the free energy barrier indicating that FiP35 is not an incipient downhill folder. The transition dynamics analysis further reveals that the folding/unfolding transition is highly heterogeneous, e.g., the transition path time varies by ∼100 fold. We identify two misfolded states and show that the dynamic heterogeneity in the folding/unfolding transitions originates from the trajectory being trapped in the misfolded and half-folded intermediate states rather than the diffusion driven by a thermal noise. The current results help reconcile the conflicting interpretations of the folding mechanism and highlight the complexity in the folding dynamics. This further motivates the need to understand the transition dynamics beyond a simple free energy picture using simulations and single-molecule experiments.

Integrated Hamiltonian Sampling: A Simple and Versatile Method for Free Energy Simulations and Conformational Sampling

Motivated by specific applications and the recent work of Gao and co-workers on integrated tempering sampling (ITS), we have developed a novel sampling approach referred to as integrated Hamiltonian sampling (IHS). IHS is straightforward to implement and complementary to existing methods for free energy simulation and enhanced configurational sampling. The method carries out sampling using an effective Hamiltonian constructed by integrating the Boltzmann distributions of a series of Hamiltonians. By judiciously selecting the weights of the different Hamiltonians, one achieves rapid transitions among the energy landscapes that underlie different Hamiltonians and therefore an efficient sampling of important regions of the conformational space. Along this line, IHS shares similar motivations as the enveloping distribution sampling (EDS) approach of van Gunsteren and co-workers, although the ways that distributions of different Hamiltonians are integrated are rather different in IHS and EDS. Specifically, we report efficient ways for determining the weights using a combination of histogram flattening and weighted histogram analysis approaches, which make it straightforward to include many end-state and intermediate Hamiltonians in IHS so as to enhance its flexibility. Using several relatively simple condensed phase examples, we illustrate the implementation and application of IHS as well as potential developments for the near future. The relation of IHS to several related sampling methods such as Hamiltonian replica exchange molecular dynamics and λ-dynamics is also briefly discussed.

Excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene. II. Ab initio multiple spawning simulations

The excited state non-adiabatic dynamics of the smallest polyene, trans 1,3-butadiene (BD), has long been the subject of controversy due to its strong coupling, ultrafast time scales and the difficulties that theory faces in describing the relevant electronic states in a balanced fashion. Here we apply Ab Initio Multiple Spawning (AIMS) using state-averaged complete active space multistate second order perturbation theory [SA-3-CAS(4/4)-MSPT2] which describes both static and dynamic electron correlation effects, providing a balanced description of both the initially prepared bright 11Bu (ππ*) state and non-adiabatically coupled dark 21Ag state of BD. Importantly, AIMS allows for on-the-fly calculations of experimental observables. We validate our approach by directly simulating the time resolved photoelectron-photoion coincidence spectroscopy results presented in Paper I [A. E. Boguslavskiy et al., J. Chem. Phys. 148, 164302 (2018)], demonstrating excellent agreement with experiment. Our simulations reveal that the initial excitation to the 11Bu state rapidly evolves via wavepacket dynamics that follow both bright- and dark-state pathways as well as mixtures of these. In order to test the sensitivity of the AIMS results to the relative ordering of states, we considered two hypothetical scenarios biased toward either the bright 1Bu or the dark 21Ag state. In contrast with AIMS/SA-3-CAS(4/4)-MSPT2 simulations, neither of these scenarios yields favorable agreement with experiment. Thus, we conclude that the excited state non-adiabatic dynamics in BD involves both of these ultrafast pathways.

3D-RISM-MP2 Approach to Hydration Structure of Pt(II) and Pd(II) Complexes: Unusual H-Ahead Mode vs Usual O-Ahead One.

Solvation of transition metal complexes with water has been one of the fundamental topics in physical and coordination chemistry. In particular, Pt(II) complexes have recently attracted considerable interest for their relation to anticancer activity in cisplatin and its analogues, yet the interaction of the water molecule and the metal center has been obscured. The challenge from a theoretical perspective remains that both the microscopic solvation effect and the dynamical electron correlation (DEC) effect have to be treated simultaneously in a reasonable manner. In this work we derive the analytical gradient for the three-dimensional reference interaction site model Møller-Plesset second order (3D-RISM-MP2) free energy. On the basis of the three-regions 3D-RISM self-consistent field (SCF) method recently proposed by us, we apply a new layer of the Z-vector method to the CP-RISM equation as well as point-charge approximation to the derivatives with respect to the density matrix elements in the RISM-CPHF equation to remarkably reduce the computational cost. This method is applied to study the interaction of H2O with the d(8) square planar transition metal complexes in aqueous solution, trans-[Pt(II)Cl2(NH3)(glycine)] (1a), [Pt(II)(NH3)4](2+) (1b), [Pt(II)(CN)4](2-) (1c), and their Pd(II) analogues 2a, 2b, and 2c, respectively, to elucidate whether the usual H2O interaction through O atom (O-ahead mode) or unusual one through H atom (H-ahead mode) is stable in these complexes. We find that the interaction energy of the coordinating water and the transition metal complex changes little when switching from gas to aqueous phase, but the solvation free energy differs remarkably between the two interaction modes, thereby affecting the relative stability of the H-ahead and O-ahead modes. Particularly, in contrast to the expectation that the O-ahead mode is preferred due to the presence of positive charges in 1b, the H-ahead mode is also found to be more stable. The O-ahead mode is found to be more stable than the H-ahead one only in 2b. The energy decomposition analysis (EDA) at the 3D-RISM-MP2 level revealed that the O-ahead mode is stabilized by the electrostatic (ES) interaction, whereas the H-ahead one is mainly stabilized by the DEC effect. The ES interaction is also responsible for the difference between the Pd(II) and Pt(II) complexes; because the electrostatic potential is more negative along the z-axis in the Pt(II) complex than in the Pd(II) one, the O-ahead mode prefers the Pd(II) complexes, whereas the H-ahead becomes predominant in the Pt(II) complexes.