Effective force field for liquid hydrogen fluoride from ab initio molecular dynamics simulation using the force-matching method

A recently developed force-matching method for obtaining effective force fields for condensed matter systems from ab initio molecular dynamics (MD) simulations has been applied to fit a simple nonpolarizable two-site pairwise force field for liquid hydrogen fluoride. The ab initio MD in this case was a Car-Parrinello (CP) MD simulation of 64 HF molecules at nearly ambient conditions within the Becke-Lee-Yang-Parr approximation to the electronic density functional theory. The force-matching procedure included a fit of short-ranged nonbonded forces, bonded forces, and atomic partial charges. The performance of the force-match potential was examined for the gas-phase dimer and for the liquid phase at various temperatures. The model was able to reproduce correctly the bent structure and energetics of the gas-phase dimer, while the results for the structural properties, self-diffusion, vibrational spectra, density, and thermodynamic properties of liquid HF were compared to both experiment and the CP MD simulation. The force-matching model performs well in reproducing nearly all of the liquid properties as well as the aggregation behavior at different temperatures. The model is computationally cheap and compares favorably to many more computationally expensive potential energy functions for liquid HF.     

Effective force fields for condensed phase systems from ab initio molecular dynamics simulation: a new method for force-matching

A novel least-squares fitting approach is presented to obtain classical force fields from trajectory and force databases produced by ab initio (e.g., Car-Parrinello) molecular dynamics (MD) simulations. The method was applied to derive effective nonpolarizable three-site force fields for liquid water at ambient conditions from Car-Parrinello MD simulations in the Becke-Lee-Yang-Parr approximation to the electronic density functional theory. The force-matching procedure includes a fit of short-ranged nonbonded forces, bonded forces, and atomic partial charges. The various parameterizations of the water force field differ by an enforced smooth cut-off applied to the short-ranged interaction term. These were obtained by fitting to the trajectory and force data produced by Car-Parrinello MD simulations of systems of 32 and 64 H(2)O molecules. The new water force fields were developed assuming both flexible or rigid molecular geometry. The simulated structural and self-diffusion properties of liquid water using the fitted force fields are in close agreement with those observed in the underlying Car-Parrinello MD simulations. The resulting empirical models compare to experiment much better than many conventional simple point charge (SPC) models. The fitted potential is also shown to combine well with more sophisticated intramolecular potentials. Importantly, the computational cost of the new models is comparable to that for SPC-like potentials.     

On the effect of a variation of the force field, spatial boundary condition and size of the QM region in QM/MM MD simulations

During the past years, the use of combined quantum-classical, QM/MM, methods for the study of complex biomolecular processes, such as enzymatic reactions and photocycles, has increased considerably. The quality of the results obtained from QM/MM calculations is largely dependent on five aspects to be considered when setting up a molecular model: the QM Hamiltonian, the MM Hamiltonian or force field, the boundary and coupling between the QM and MM regions, the size of the QM region and the boundary condition for the MM region. In this study, we systematically investigate the influence of a variation of the molecular mechanics force field and the size of the QM region in QM/MM MD simulations on properties of the photoactive part of the blue light photoreceptor protein AppA. For comparison, we additionally performed classical MD simulations and studied the effect of a variation of the type of spatial boundary condition. The classical boundary conditions and the force field used in a QM/MM MD simulation are shown to have non-neglegible effects upon the structural and energetic properties of the protein which makes it advisable to minimize computational artifacts in QM/MM MD simulations by application of periodic boundary conditions and a thermodynamically calibrated force field. A comparison of the structural and energetic properties of MD simulations starting from two alternative, different X-ray structures for the blue light utilizing flavin protein in its dark state indicates a slight preference of the two force fields used for the so-called Anderson structure over the Jung structure.     

Ab initio quantum mechanical charge field (QMCF) molecular dynamics: a QM/MM – MD procedure for accurate simulations of ions and complexes

A new formalism for quantum mechanical / molecular mechanical (QM/MM) dynamics of chemical species in solution has been developed, which does not require the construction of any other potential functions except those for solvent–solvent interactions, maintains all the advantages of large simulation boxes and ensures the accuracy of ab initio quantum mechanics for all forces acting in the chemically most relevant region. Interactions between solute and more distant solvent molecules are incorporated by a dynamically adjusted force field corresponding to the actual molecular configuration of the simulated system and charges derived from the electron distribution in the solvate. The new formalism has been tested with some examples of hydrated ions, for which accurate conventional ab initio QM/MM simulations have been previously performed, and the comparison shows equivalence and in some aspects superiority of the new method. As this simulation procedure does not require any tedious construction of two-and three-body interaction potentials inherent to conventional QM/MM approaches, it opens the straightforward access to ab initio molecular dynamics simulations of any kind of solutes, such as metal complexes and other composite species in solution.     

Achieving fast convergence of ab initio free energy perturbation calculations with the adaptive force-matching method

This paper studies the possibility of improving the convergence of ab initio free energy perturbation (FEP) calculations by developing customized force fields with the adaptive force-matching (AFM) method. The ab initio FEP method relies on a molecular mechanics (MM) potential to sample configuration space. If the Boltzmann weight of the MM sampling is close to that of the ab initio method, the efficiency of ab initio FEP will be optimal. The difference in the Boltzmann weights can be quantified by the relative energy difference distribution (REDD). The force field developed through AFM significantly improves the REDD when compared with standard MM models, thus improving the convergence of the ab initio FEP calculation. The static dielectric constant ε_s of ice-Ih was studied with PW-91 through ab initio FEP. With a customized force field developed through AFM, we were able to converge ε_s to 80 ± 4 with 3,600 configurations. A similar ab initio FEP calculation with the TIP4P model would require 220 times more configurations to achieve the same accuracy. Our study indicates that the PW-91 functional underestimates ice-Ih ε_s by about 20%.     

Structure of liquid water at ambient temperature from ab initio molecular dynamics performed in the complete basis set limit

Structural properties of liquid water at ambient temperature were studied using Car-Parrinello [Phys. Rev. Lett. 55, 2471 (1985)] ab initio molecular dynamics (CPAIMD) simulations combined with the Kohn-Sham (KS) density functional theory and the BLYP exchange-correlation functional for the electronic structure. Unlike other recent work on the same subject, where plane-wave (PW) or hybrid Gaussian/plane-wave basis sets were employed, in the present paper, a discrete variable representation (DVR) basis set is used to expand the KS orbitals, so that with the real-space grid adapted in the present work, the properties of liquid water could be obtained very near the complete basis set limit. Structural properties of liquid water were extracted from a 30 ps CPAIMD-BLYP/DVR trajectory at 300 K. The radial distribution functions (RDFs), spatial distribution functions, and hydrogen bond geometry obtained from the CPAIMD-BLYP/DVR simulation are generally in good agreement with the most up to date experimental measurements. Compared to recent ab initio MD simulations based on PW basis sets, less significant overstructuring was found in the RDFs and the distributions of hydrogen bond angles, suggesting that previous plane-wave and Gaussian basis set calculations have exaggerated the tendency toward overstructuring.     

The quest for the best nonpolarizable water model from the adaptive force matching method

The recently introduced adaptive force matching (AFM) method is used to develop a significantly improved pair‐wise nonpolarizable potential for water. A rigid version of the potential is also presented to enable larger time steps for biological simulations. In this work, it is demonstrated that the AFM method can be used to systematically assess the importance of each functional term during the construction of a force field. For a water potential, it is established that a single off‐atom charge center (M) in the plane of water outperforms two out‐of‐plane charge sites for reproducing intermolecular forces. The four‐site pair‐wise nonpolarizable force field developed in this work rivals some of the most sophisticated polarizable models in terms of reproducing accurate ab initio forces. The force fields are parameterized to perform best in the temperature range from 0 to 40°C. Equilibrium and dynamical properties calculated with the flexible and rigid force fields are in good agreement with experimental results. For the flexible model, the agreement improves when path integral simulation is performed. These force fields provide high‐quality results at a very low computational cost and are thus well suited to atomistic scale biological simulations. The AFM method provides a mechanism for selecting important terms in force field expressions and is a very promising tool for producing accurate force fields in condensed phases. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

Multireference ab initio quantum mechanics/molecular mechanics study on intermediates in the catalytic cycle of cytochrome P450(cam)

We have investigated the elusive reactive species of cytochrome P450(cam) (Compound I), the hydroxo complex formed during camphor hydroxylation, and the ferric hydroperoxo complex (Compound 0) by combined quantum mechanical/molecular mechanical (QM/MM) calculations, employing both density functional theory (DFT) and correlated ab initio methods. The first two intermediates appear multiconfigurational in character, especially in the doublet state and less so in the quartet state. DFT(B3LYP)/MM calculations reproduce the relative energies from correlated ab initio QM/MM treatments quite well, except for the splitting of the lowest A(1u)-A(2u) radical states. The inclusion of dynamic correlation is crucial for the proper ab initio treatment of these intermediates.     

New force field for molecular simulation of guanidinium-based ionic liquids

An all-atom force field was proposed for a new class of room temperature ionic liquids (RTILs), N,N,N',N'-tetramethylguanidinium (TMG) RTILs. The model is based on the AMBER force field with modifications on several parameters. The refinements include (1) fitting the vibration frequencies for obtaining force coefficients of bonds and angles against the data obtained by ab initio calculations and/or by experiments and (2) fitting the torsion energy profiles of dihedral angles for obtaining torsion parameters against the data obtained by ab initio calculations. To validate the force field, molecular dynamics (MD) simulations at different temperatures were performed for five kinds of RTILs, where TMG acts as a cation and formate, lactate, perchlorate, trifluoroacetate, and trifluoromethylsulfonate act as anions. The predicted densities were in good agreement with the experimental data. Radial distribution functions (RDFs) and spatial distribution functions (SDFs) were investigated to depict the microscopic structures of the RTILs.     

Force-field parameters for the simulation of tetrahedral intermediates of serine hydrolases

CHARMM force-field parameters are reported for the tetrahedral intermediate of serine hydrolases. The fitting follows the standard protocol proposed for CHARMM22. The reference data include ab initio (RHF/6-31G*) interaction energies of complexes between water and the model compound 1,1-dimethoxyethoxide, torsional profiles of related model compounds from correlated ab initio (MP2/6-311+G*//B3LYP/6-31+G*) calculations, as well as molecular geometries and vibrational frequencies from density functional theory (B3LYP/6-31+G*). The optimized parameters reproduce the target data well. Their utility is demonstrated by a QM/MM study of the tetrahedral intermediate in Bacillus subtilis lipase A, and by classical molecular modeling of enantioselectivity in Pseudomonas aeruginosa lipase and its mutants.     

An extensible interface for QM/MM molecular dynamics simulations with AMBER

We present an extensible interface between the AMBER molecular dynamics (MD) software package and electronic structure software packages for quantum mechanical (QM) and mixed QM and classical molecular mechanical (MM) MD simulations within both mechanical and electronic embedding schemes. With this interface, ab initio wave function theory and density functional theory methods, as available in the supported electronic structure software packages, become available for QM/MM MD simulations with AMBER. The interface has been written in a modular fashion that allows straight forward extensions to support additional QM software packages and can easily be ported to other MD software. Data exchange between the MD and QM software is implemented by means of files and system calls or the message passing interface standard. Based on extensive tests, default settings for the supported QM packages are provided such that energy is conserved for typical QM/MM MD simulations in the microcanonical ensemble. Results for the free energy of binding of calcium ions to aspartate in aqueous solution comparing semiempirical and density functional Hamiltonians are shown to demonstrate features of this interface. © 2013 Wiley Periodicals, Inc.     

Classical force field parameters for the heme prosthetic group of cytochrome c

Accurate force fields are essential for describing biological systems in a molecular dynamics simulation. To analyze the docking of the small redox protein cytochrome c (cyt c) requires simulation parameters for the heme in both the reduced and oxidized states. This work presents parameters for the partial charges and geometries for the heme in both redox states with ligands appropriate to cyt c. The parameters are based on both protein X-ray structures and ab initio density functional theory (DFT) geometry optimizations at the B3LYP/6-31G* level. The simulations with the new parameter set reproduce the geometries of the X-ray structures and the interaction energies between water and heme prosthetic group obtained from B3LYP/6-31G* calculations. The parameter set developed here will provide new insights into docking processes of heme containing redox proteins.     

The influence of the Jahn-Teller effect and of heteroligands on the reactivity of Cu2+

Experimentally hardly accessible Jahn-Teller inversions and the influence of heteroligands on the reactivity of Cu2+ are characterized by ab initio QM/MM MD simulations of Cu2+ ion and its amino complexes in water.     

Solvent effects on peroxynitrite structure and properties from QM/MM simulations

We have investigated the structure and the vibrational spectrum of peroxynitrite anion in aqueous solution by means of combined quantum-classical (QM/MM) molecular dynamics simulations. In our QM/MM scheme, the reactant was modeled using density functional theory with a Gaussian basis set and the solvent was described using the mean-field TIP4P and the polarizable TIP4P-FQ force fields. The choice of basis sets, functionals and force field parameters has been validated by performing calculations on isolated peroxynitrite and on small peroxynitrite-water complexes. Poor values for isolated peroxynitrite structural properties and vibrational frequencies are found for most ab initio methods, particularly regarding the ON-OO(-) bond distance and the harmonic stretching frequency, probably due to the singlet-triplet instability found in the HF wave function. On the other hand, DFT methods yield results in better agreement with high level CCSD(T) ab initio calculations. We have computed the vibrational spectrum for aqueous peroxynitrite by calculating the Fourier transform of the velocity autocorrelation function extracted from the QM-MM molecular dynamics simulations. Our computational scheme, which allows for the inclusion of both anharmonicity and solvent effects, is able to clarify previous discrepancies regarding the experimental spectra assignments and to shed light on the subtle interplay between solvation and peroxynitrite structure and properties.