Abstract. The self-consistent decay of mixing (SCDM) semiclassical trajectory method for electronically nonadiabatic dynamics is improved by modifying the switching probability that determines the instantaneous electronic state toward which the system decoheres. The new method is called coherent switching with decay of mixing (CSDM), and it differs from the previously presented SCDM method in that the electronic amplitudes controlling the switching of the decoherent state are treated fully coherently in the electronic equations of motion for each complete passage through a strong interaction region. The new method is tested against accurate quantum mechanical calculations for twelve atom-diatom scattering test cases. Also tested are the SCDM method and the trajectory surface hopping method of Parlant and Gislason that requires coherent passages through each strong interaction region, and which we call the ECP-TSH method. The results are compared with previously presented results for the fewest-switches with time uncertainty and Tully's fewest switches (TFS) surface hopping methods and the semiclassical Ehrenfest method. We find that the CSDM method is the most accurate of the semiclassical trajectory methods tested. Including coherent passages improves the accuracy of the SCDM method (i.e., the CSDM method is more accurate than the SCDM method) but not of the trajectory surface hopping method (i.e., the ECP-TSH method is not more accurate on average than the TFS method).

Electronically nonadiabatic or non-Born-Oppenheimer (non-BO) chemical processes (photodissociation, charge-transfer, etc.) involve a nonradiative change in the electronic state of the system. Molecular dynamics simulations typically treat nuclei as moving classically on a single adiabatic potential energy surface, and these techniques are not immediately generalizable to non-BO systems due to the inherently quantum mechanical nature of electronic transitions. Here we generalize the concept of a single-surface molecular dynamics trajectory to that of a coupled-surface non-BO trajectory that evolves "semiclassically" under the influence of two or more electronic states and their couplings. Five non-BO trajectory methods are discussed. Next, we summarize the results of a series of systematic studies using a database of accurate quantum mechanical reaction probabilities and internal energy distributions for several six-dimensional model bimolecular scattering collisions. The test set includes three kinds of prototypical nonadiabatic interactions: conical intersections, avoided crossings, and regions of weak coupling. We show that the coherent switching with decay of mixing (CSDM) non-BO trajectory method provides a robust and accurate way to extend molecular dynamics to treat electronically nonadiabatic chemistry for all three kinds of nonadiabatic interactions, and we recommend it for molecular dynamics simulations involving nonradiative electronic state changes.

Recent progress in the theoretical treatment of electronically nonadiabatic processes is discussed. First we discuss the generalized Born-Oppenheimer approximation, which identifies a subset of strongly coupled states, and the relative advantages and disadvantages of adiabatic and diabatic representations of the coupled surfaces and their interactions are considered. Ab initio diabatic representations that do not require tracking geometric phases or calculating singular nonadiabatic nuclear momentum coupling will be presented as one promising approach for characterizing the coupled electronic states of polyatomic photochemical systems. Such representations can be accomplished by methods based on functionals of the adiabatic electronic density matrix and the identification of reference orbitals for use in an overlap criterion. Next, four approaches to calculating or modeling electronically nonadiabatic dynamics are discussed: (1) accurate quantum mechanical scattering calculations, (2) approximate wave packet methods, (3) surface hopping, and (4) self-consistent-potential semiclassical approaches. The last two of these are particularly useful for polyatomic photochemistry, and recent refinements of these approaches will be discussed. For example, considerable progress has been achieved in making the surface hopping method more applicable to the study of systems with weakly coupled electronic states. This includes introducing uncertainty principle considerations to alleviate the problem of classically forbidden surface hops and the development of an efficient sampling algorithm for low-probability events. A topic whose central importance in a number of quantum mechanical fields is becoming more widely appreciated is the introduction of decoherence into the quantal degrees of freedom to account for the effect of the classical treatment on the other degrees of freedom, and we discuss how the introduction of such decoherence into a self-consistent-potential approximation leads to a reasonably accurate but very practical trajectory method for electronically nonadiabatic processes. Finally, the performances of several dynamical methods for Landau-Zener-type and Rosen-Zener-Demkov-type reactive scattering problems are compared.

Nanotoxicity is becoming a major concern as the use of nanoparticles in imaging, therapeutics, diagnostics, catalysis, sensing, and energy harvesting continues to grow dramatically. The tunable functionalities of the nanoparticles offer unique chemical interactions in the translocation process through cell membranes. The overall translocation rate of the nanoparticle can vary immensely on the basis of the charge of the surface functionalization along with shape and size. Using advanced molecular dynamics simulation techniques, we compute translocation rate constants of functionalized cone-, cube-, rod-, rice-, pyramid-, and sphere-shaped nanoparticles through lipid membranes. The computed results indicate that depending on the nanoparticle shape and surface functionalization charge, the translocation rates can span 60 orders of magnitude. Unlike isotropic nanoparticles, positively charged, faceted, rice-shaped nanoparticles undergo electrostatics-driven reorientation in the vicinity of the membrane to maximize their contact area and translocate instantaneously, disrupting lipid self-assembly and thereby causing significant membrane damage. In contrast, negatively charged nanoparticles are electrostatically repelled from the cell membrane and are less likely to translocate. Differences in translocation rates among various shapes may have implications on the structural evolution of pathogens from spherical to rodlike morphologies for enhanced efficacy.

In this computational study, we present the dissolution rates for quartz as a function of pH at 298 K. At any given pH, the dissolution of the quartz surface depends on the distribution of protonated, deprotonated, or neutral species. The dissolution mechanism for each of these three species was investigated by ab initio electronic structure calculations to obtain the reaction profile. Using the barrier height along with the partition functions for the transition state and the reactants in the rate-limiting steps, we calculated the TST rate constants for the reactions for the temperature range of 200-500 K. At 298 K the rate constant (s-1) for the dissolution of neutral species was found to be several orders of magnitude smaller than the rate-limiting steps for the protonated and deprotonated species. The values of the rate constants were used in the rate law expression to calculate the overall dissolution rate (mol m-2 s-1) at a given pH. The calculated rates were compared to previously reported experimental and theoretical rates and were found to be in good agreement over 2-12 pH range.

Tight junctions (TJs) are key players in determining tissue-specific paracellular permeability across epithelial and endothelial membranes. Claudin proteins, the primary determinants of TJs structure and functionality, assemble in paracellular spaces to form channels and pores that are charge and size selective. Here, using molecular dynamics (MD) simulations, we elucidate the molecular assembly of claudin-3 and claudin-5 proteins of blood-brain barrier TJs. Despite having a high degree of sequence and structural similarity, these two claudins form different types of cis-interactions. Molecular docking of the observed cis-interfaces into trans-forms revealed two putative pore models that were also observed in the self-assembly simulations. The observed pore structures (pore I and II) have pore-lining residues that have been previously reported in the literature. The pore I model is consistent with a previously reported claudin-15 model. The pore II model, also consistent with biochemical results, has not been reported previously. Further analysis using in silico site-directed mutations provide convincing support for the validity of the pore II model. Using steered MD and umbrella sampling, we computed the transport properties of water and α-d-glucose through pore II. The study offers new insight into the selectivity of blood-brain barrier TJs.

The blood-brain barrier (BBB) constituted by claudin-5 tight junctions is critical in maintaining the homeostasis of the central nervous system, but this highly selective molecular interface is an impediment for therapeutic interventions in neurodegenerative and neurological diseases. Therapeutic strategies that can exploit the paracellular transport remain elusive due to lack of molecular insights of the tight junction assembly. This study focuses on analyzing the membrane driven cis interactions of claudin-5 proteins in the formation of the BBB tight junctions. We have adopted a synergistic approach employing in silico multiscale dynamics and in vitro cross-linking experiments to study the claudin-5 interactions. Long time scale simulations of claudin-5 monomers, in seven different lipid compositions, show formation of cis dimers that subsequently aggregate into strands. In vitro formaldehyde cross-linking studies also conclusively show that cis-interacting claudin-5 dimers cross-link with short methylene spacers. Using this synergistic approach, we have identified five unique dimer interfaces in our simulations that correlate with the cross-linking experiments, four of which are mediated by transmembrane (TM) helices and the other mediated by extracellular loops (ECL). Potential of mean force calculations of these five dimers revealed that the TM mediated interfaces, which can have distinctive leucine zipper interactions in some cases, are more stable than the ECL mediated interface. Additionally, simulations show that claudin-5 dimerization is significantly influenced by the lipid microenvironment. This study captures the fundamental interactions responsible for the BBB tight junction assembly and offers a framework for extending this work to other tight junctions found in the body.

The cell envelope of Gram-negative bacteria contains a lipopolysaccharide (LPS) rich outer membrane that acts as the first line of defense for bacterial cells in adverse physical and chemical environments. The LPS macromolecule has a negatively charged oligosaccharide domain that acts as an ionic brush, limiting the permeability of charged chemical agents through the membrane. Besides the LPS, the outer membrane has radially extending O-antigen polysaccharide chains and β-barrel membrane proteins that make the bacterial membrane physiologically unique compared to phospholipid cell membranes. Elucidating the interplay of these contributing macromolecular components and their role in the integrity of the bacterial outer membrane remains a challenge. To bridge the gap in our current understanding of the Gram-negative bacterial membrane, we have developed a coarse grained force field for outer membrane that is computationally affordable for simulating dynamical process over physiologically relevant time scales. The force field was benchmarked against available experimental and atomistic simulations data for properties such as membrane thickness, density profiles of the residues, area per lipid, gel to liquid-crystalline phase transition temperatures, and order parameters. More than 17 membrane compositions were studied with a combined simulation time of over 100 μs. A comparison of simulated structural and dynamical properties with corresponding experimental data shows that the developed force field reproduces the overall physiology of LPS rich membranes. The affordability of the developed model for long time scale simulations can be instrumental in determining the mechanistic aspects of the antimicrobial action of chemical agents as well as assist in designing antimicrobial peptides with enhanced outer membrane permeation properties.