Spontaneous-search method and short-time dynamics: applications to the Domany-Kinzel cellular automaton

The one-dimensional Domany-Kinzel cellular automaton is investigated by two numerical approaches: (i) the spontaneous-search method, which is a method appropriated for a search of criticality; (ii) short-time dynamics. Both critical frontiers of the system are investigated, namely, the one separating the frozen and active phases, as well as the critical line determined by damage spreading between two cellular automata, that splits the active phase into the nonchaotic and chaotic phases. The efficiency of the spontaneous-search method is established herein through a precise estimate of both critical frontiers, and in addition to that, it is shown that this method may also be used in the determination of the critical exponent ν_⊥. Using the critical frontiers obtained, other exponents are estimated through short-time dynamics. It is verified that the critical exponents of both critical frontiers fall in the universality class of directed percolation.     

PCMSolver: An open-source library for solvation modeling

PCMSolver is an open-source library for continuum electrostatic solvation. It can be combined with any quantum chemistry code and requires a minimal interface with the host program, greatly reducing programming effort. As input, PCMSolver needs only the molecular geometry to generate the cavity and the expectation value of the molecular electrostatic potential on the cavity surface. It then returns the solvent polarization back to the host program. The design is powerful and versatile: minimal loss of performance is expected, and a standard single point self-consistent field implementation requires no more than 2 days of work. We provide a brief theoretical overview, followed by two tutorials: one aimed at quantum chemistry program developers wanting to interface their code with PCMSolver , the other aimed at contributors to the library. We finally illustrate past and ongoing work, showing the library's features, combined with several quantum chemistry programs.     

Computational Prediction of 1H and 13C NMR Chemical Shifts for Protonated Alkylpyrroles: Electron Correlation and Not Solvation is the Salvation

Prediction of chemical shifts in organic cations is known to be a challenge. In this article we meet this challenge for α-protonated alkylpyrroles, a class of compounds not yet studied in this context, and present a combined experimental and theoretical study of the ¹³C and ¹H chemical shifts in three selected pyrroles. We have investigated the importance of the solvation model, basis set, and quantum chemical method with the goal of developing a simple computational protocol, which allows prediction of ¹³C and ¹H chemical shifts with sufficient accuracy for identifying such compounds in mixtures. We find that density functional theory with the B3LYP functional is not sufficient for reproducing all ¹³C chemical shifts, whereas already the simplest correlated wave function model, Møller–Plesset perturbation theory (MP2), leads to almost perfect agreement with the experimental data. Treatment of solvent effects generally improves the agreement with experiment to some extent and can in most cases be accomplished by a simple polarizable continuum model. The only exception is the NH proton, which requires inclusion of explicit solvent molecules in the calculation.     

On the preferential solvation of drugs and PAHs in binary solvent mixtures

The preferential solvation parameters, i.e., the differences between the local and bulk mole fractions of the solvents in solutions of certain drugs and polycyclic aromatic hydrocarbons (PAHs) are derived from their solubilities in binary solvent mixtures by means of the inverse Kirkwood-Buff integral (IKBI) and the quasi-lattice quasi-chemical (QLQC) methods. The solutes include caffeine, niflumic acid, diazepam, benzocaine, phenacetin, paracetamol, nalidixic acid, anthracene, and tr-stilbene and both aqueous and non-aqueous mixtures are considered. The findings are rationalized in terms of the interactions between the solute and solvents and the solvent components among themselves.     

Thermodynamics based on the principle of least abbreviated action: Entropy production in a network of coupled oscillators

We present some novel thermodynamic ideas based on the Maupertuis principle. By considering Hamiltonians written in terms of appropriate action-angle variables we show that thermal states can be characterized by the action variables and by their evolution in time when the system is nonintegrable. We propose dynamical definitions for the equilibrium temperature and entropy as well as an expression for the nonequilibrium entropy valid for isolated systems with many degrees of freedom. This entropy is shown to increase in the relaxation to equilibrium of macroscopic systems with short-range interactions, which constitutes a dynamical justification of the Second Law of Thermodynamics. Several examples are worked out to show that this formalism yields the right microcanonical (equilibrium) quantities. The relevance of this approach to nonequilibrium situations is illustrated with an application to a network of coupled oscillators (Kuramoto model). We provide an expression for the entropy production in this system finding that its positive value is directly related to dissipation at the steady state in attaining order through synchronization.     

Steady state statistics of driven diffusions

We consider overdamped diffusion processes driven out of thermal equilibrium and we analyze their dynamical steady fluctuations. We discuss the thermodynamic interpretation of the joint fluctuations of occupation times and currents; they incorporate respectively the time-symmetric and the time-antisymmetric sector of the fluctuations. We highlight the canonical structure of the joint fluctuations. The novel concept of traffic complements the entropy production for the study of the occupation statistics. We explain how the occupation and current fluctuations get mutually coupled out of equilibrium. Their decoupling close-to-equilibrium explains the validity of entropy production principles.     

Three‐dimensional structure of cyclic antibiotic teicoplanin aglycone using NMR distance and dihedral angle restraints in a DMSO solvation model

The three‐dimensional solution conformation of teicoplanin aglycone was determined using NMR spectroscopy. A combination of NOE and dihedral angle restraints in a DMSO solvation model was used to calculate an ensemble of structures having a root mean square deviation of 0.17 Å. The structures were generated using systematic searches of conformational space for optimal satisfaction of distance and dihedral angle restraints. Comparison of the NMR‐derived structure of teicoplanin aglycone with the X‐ray structure of a teicoplanin aglycone analog revealed a common backbone conformation with deviation of two aromatic side chain substituents. Experimentally determined backbone ¹³C chemical shifts showed good agreement with those computed at the density functional level of theory, providing a cross validation of the backbone conformation. The flexible portion of the molecule was consistent with the region that changes conformation to accommodate protein binding. The results showed that a hydrogen‐bonded DMSO molecule in combination with NMR‐derived restraints together enabled calculation of structures that satisfied experimental data. Copyright © 2015 John Wiley & Sons, Ltd.     

Fragment‐based quantum mechanical calculation of protein–protein binding affinities

The electrostatically embedded generalized molecular fractionation with conjugate caps (EE‐GMFCC) method has been successfully utilized for efficient linear‐scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE‐GMFCC method for calculation of binding affinity of Endonuclease colicin–immunity protein complex. The binding free energy changes between the wild‐type and mutants of the complex calculated by EE‐GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6‐31G*‐D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein–protein binding affinities. Moreover, the self‐consistent calculation of PB solvation energy is required for accurate calculations of protein–protein binding free energies. This study demonstrates that the EE‐GMFCC method is capable of providing reliable prediction of relative binding affinities for protein–protein complexes. © 2018 Wiley Periodicals, Inc.     

A refined cavity construction algorithm for the conductor‐like screening model

A cavity construction algorithm based on the triangulation of an iso‐surface is introduced as a new standard for dielectric continuum solvation calculations with the Conductor‐like Screening Model COSMO. It overcomes deficiencies which have become apparent for the original COSMO standard cavity, especially in concave regions of the molecular shaped cavity. The new standard, called FINE Cavity, is described in this article with several application examples. The earlier COSMO cavity construction algorithms are described for comparison. © 2018 Wiley Periodicals, Inc.     

Combining the polarizable Drude force field with a continuum electrostatic Poisson–Boltzmann implicit solvation model

In this work, we have combined the polarizable force field based on the classical Drude oscillator with a continuum Poisson–Boltzmann/solvent‐accessible surface area (PB/SASA) model. In practice, the positions of the Drude particles experiencing the solvent reaction field arising from the fixed charges and induced polarization of the solute must be optimized in a self‐consistent manner. Here, we parameterized the model to reproduce experimental solvation free energies of a set of small molecules. The model reproduces well‐experimental solvation free energies of 70 molecules, yielding a root mean square difference of 0.8 kcal/mol versus 2.5 kcal/mol for the CHARMM36 additive force field. The polarization work associated with the solute transfer from the gas‐phase to the polar solvent, a term neglected in the framework of additive force fields, was found to make a large contribution to the total solvation free energy, comparable to the polar solute–solvent solvation contribution. The Drude PB/SASA also reproduces well the electronic polarization from the explicit solvent simulations of a small protein, BPTI. Model validation was based on comparisons with the experimental relative binding free energies of 371 single alanine mutations. With the Drude PB/SASA model the root mean square deviation between the predicted and experimental relative binding free energies is 3.35 kcal/mol, lower than 5.11 kcal/mol computed with the CHARMM36 additive force field. Overall, the results indicate that the main limitation of the Drude PB/SASA model is the inability of the SASA term to accurately capture non‐polar solvation effects. © 2018 Wiley Periodicals, Inc.