Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods.

The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.

Large variation of vacancy formation energies in the surface of crystalline ice.

Resolving the atomic structure of the surface of ice particles within clouds, over the temperature range encountered in the atmosphere and relevant to understanding heterogeneous catalysis on ice, remains an experimental challenge. By using first-principles calculations, we show that the surface of crystalline ice exhibits a remarkable variance in vacancy formation energies, akin to an amorphous material. We find vacancy formation energies as low as ~0.1-0.2 eV, which leads to a higher than expected vacancy concentration. Because a vacancy's reactivity correlates with its formation energy, ice particles may be more reactive than previously thought. We also show that vacancies significantly reduce the formation energy of neighbouring vacancies, thus facilitating pitting and contributing to pre-melting and quasi-liquid layer formation. These surface properties arise from proton disorder and the relaxation of geometric constraints, which suggests that other frustrated materials may possess unusual surface characteristics.

Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations.

Caspases are fundamental targets for pharmaceutical interventions in a variety of diseases involving disregulated apoptosis. Here, we present a quantum mechanics/molecular mechanics Car-Parrinello study of key steps of the enzymatic reaction for a representative member of this family, caspase-3. The hydrolysis of the acyl-enzyme complex is described at the density functional (BLYP) level of theory while the protein frame and solvent are treated using the GROMOS96 force field. These calculations show that the attack of the hydrolytic water molecule implies an activation free energy of ca. DeltaF(A) approximately equal 19 +/- 4 kcal/mol in good agreement with experimental data and leads to a previously unrecognized gem-diol intermediate that can readily (DeltaF(A) approximately equal 5 +/- 3 kcal/mol) evolve to the enzyme products. Our findings assist in elucidating the striking difference in catalytic activity between caspases and other structurally well-characterized cysteine proteases (papains and cathepsins) and may help design novel transition-state analog inhibitors.

Cis-trans isomerization in triply-bonded ditungsten complexes: a multitude of possible pathways.

We have investigated different possible mechanisms for the cis-trans isomerization in triply bonded ditungsten complexes with stoichiometry W(2)Cl(4)(NHEt)(2)(PMe(3))(2) using static density functional calculations as well as Car-Parrinello simulations. Our studies reveal an unexpected richness of possible reaction pathways that include both unimolecular and bimolecular mechanisms. Among the possible routes that have been identified are processes involving successive dissociation/reassociation of phosphine ligands, intramolecular chloride hopping, intertungsten phosphine exchange as well as numerous combinations of these basic reaction types. All pathways involve maximal activation barriers of less than 35 kcal/mol and include phosphine concentration dependent and independent routes. The energetically most favorable phosphine-dependent pathway is based on the dissociation/reassociation of phosphine ligands. This path is characterized by a maximal dissociation barrier of 18 kcal/mol. The fastest alternative unimolecular route (with a maximal activation barrier of 24 kcal/mol) is based on a direct exchange of phosphine between the two metallic coordination centers. All the identified pathways, with the exception of a previously proposed internal flip mechanism that can be ruled out on energetic grounds, are competitive and may contribute in various combinations to the overall reaction rate. The identified isomerization mechanisms are fully consistent with the experimentally observed 3-state-kinetics and the dependence of the overall reaction rate on the excess concentration of phosphine which is demonstrated with a simplified kinetic model of the process.