Using molecular dynamics and quantum mechanics calculations to model fluorescence observables

We provide a critical examination of two different methods for generating a donor-acceptor electronic coupling trajectory from a molecular dynamics (MD) trajectory and three methods for sampling that coupling trajectory, allowing the modeling of experimental observables directly from the MD simulation. In the first coupling method we perform a single quantum-mechanical (QM) calculation to characterize the excited state behavior, specifically the transition dipole moment, of the fluorescent probe, which is then mapped onto the configuration space sampled by MD. We then utilize these transition dipoles within the ideal dipole approximation (IDA) to determine the electronic coupling between the probes that mediates the transfer of energy. In the second method we perform a QM calculation on each snapshot and use the complete transition densities to calculate the electronic coupling without need for the IDA. The resulting coupling trajectories are then sampled using three methods ranging from an independent sampling of each trajectory point (the independent snapshot method) to a Markov chain treatment that accounts for the dynamics of the coupling in determining effective rates. The results show that the IDA significantly overestimates the energy transfer rate (by a factor of 2.6) during the portions of the trajectory in which the probes are close to each other. Comparison of the sampling methods shows that the Markov chain approach yields more realistic observables at both high and low FRET efficiencies. Differences between the three sampling methods are discussed in terms of the different mechanisms for averaging over structural dynamics in the system. Convergence of the Markov chain method is carefully examined. Together, the methods for estimating coupling and for sampling the coupling provide a mechanism for directly connecting the structural dynamics modeled by MD with fluorescence observables determined through FRET experiments.     

Geometry optimization based on linear response free energy with quantum mechanical/molecular mechanical method: applications to Menshutkin-type and Claisen rearrangement reactions in aqueous solution

The authors present a method based on a linear response theory that allows one to optimize the geometries of quantum mechanical/molecular mechanical (QM/MM) systems on the free energy surfaces. Two different forms of linear response free energy functionals are introduced, and electronic wave functions of the QM region, as well as the responses of electrostatic and Lennard-Jones potentials between QM and MM regions, are self-consistently determined. The covariant matrix relating the QM charge distribution to the MM response is evaluated by molecular dynamics (MD) simulation of the MM system. The free energy gradients with respect to the QM atomic coordinates are also calculated using the MD trajectory results. They apply the present method to calculate the free energy profiles of Menshutkin-type reaction of NH3 with CH3Cl and Claisen rearrangement of allyl vinyl ether in aqueous solution. For the Menshutkin reaction, the free energy profile calculated with the modified linear response free energy functional is in good agreement with that by the free energy perturbation calculations. They examine the nonequilibrium solvation effect on the transmission coefficient and the kinetic isotope effect for the Claisen rearrangement.     

QM/MM calculation of solvent effects on absorption spectra of guanine

Electronic spectra of guanine in the gas phase and in water were studied by quantum mechanical/molecular mechanical (QM/MM) methods. Geometries for the excited‐state calculations were extracted from ground‐state molecular dynamics (MD) simulations using the self‐consistent‐charge density functional tight binding (SCC‐DFTB) method for the QM region and the TIP3P force field for the water environment. Theoretical absorption spectra were generated from excitation energies and oscillator strengths calculated for 50 to 500 MD snapshots of guanine in the gas phase (QM) and in solution (QM/MM). The excited‐state calculations used time‐dependent density functional theory (TDDFT) and the DFT‐based multireference configuration interaction (DFT/MRCI) method of Grimme and Waletzke, in combination with two basis sets. Our investigation covered keto‐N7H and keto‐N9H guanine, with particular focus on solvent effects in the low‐energy spectrum of the keto‐N9H tautomer. When compared with the vertical excitation energies of gas‐phase guanine at the optimized DFT (B3LYP/TZVP) geometry, the maxima in the computed solution spectra are shifted by several tenths of an eV. Three effects contribute: the use of SCC‐DFTB‐based rather than B3LYP‐based geometries in the MD snapshots (red shift of ca. 0.1 eV), explicit inclusion of nuclear motion through the MD snapshots (red shift of ca. 0.1 eV), and intrinsic solvent effects (differences in the absorption maxima in the computed gas‐phase and solution spectra, typically ca. 0.1–0.3 eV). A detailed analysis of the results indicates that the intrinsic solvent effects arise both from solvent‐induced structural changes and from electrostatic solute–solvent interactions, the latter being dominant. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

Development of massive multilevel molecular dynamics simulation program,platypus (PLATform for dYnamic protein unified simulation), for the elucidation of protein functions

A massively parallel program for quantum mechanical‐molecular mechanical (QM/MM) molecular dynamics simulation, called Platypus (PLATform for dYnamic Protein Unified Simulation), was developed to elucidate protein functions. The speedup and the parallelization ratio of Platypus in the QM and QM/MM calculations were assessed for a bacteriochlorophyll dimer in the photosynthetic reaction center (DIMER) on the K computer, a massively parallel computer achieving 10 PetaFLOPs with 705,024 cores. Platypus exhibited the increase in speedup up to 20,000 core processors at the HF/cc‐pVDZ and B3LYP/cc‐pVDZ, and up to 10,000 core processors by the CASCI(16,16)/6‐31G** calculations. We also performed excited QM/MM‐MD simulations on the chromophore of Sirius (SIRIUS) in water. Sirius is a pH‐insensitive and photo‐stable ultramarine fluorescent protein. Platypus accelerated on‐the‐fly excited‐state QM/MM‐MD simulations for SIRIUS in water, using over 4000 core processors. In addition, it also succeeded in 50‐ps (200,000‐step) on‐the‐fly excited‐state QM/MM‐MD simulations for the SIRIUS in water. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

Parallel variable selection of molecular dynamics clusters as a tool for calculation of spectroscopic properties

Clusters of a solute and a few solvent molecules obtained from molecular dynamics (MD) are a powerful tool to study solvation effects by advanced quantum chemical (QC) methods. For spectroscopic properties strongly dependent on the solvation, however, a large number of clusters are needed for a good convergence. In this work, a parallel variable selection (PVS) method is proposed that in some cases efficiently reduces the number of clusters needed for the averaging. The mass, charge, or atomic density MD distributions are used as a secondary variable to preselect the most probable cluster geometries used for averaging of solute spectral properties. When applied to nuclear magnetic resonance chemical shift of a model alcohol, the method allowed one to significantly reduce the total computational time, by a factor of 10. Even larger savings were achieved for the modeling of Raman and Raman optical activity spectra of (S)‐lactamide molecule dissolved in water. The results thus suggest that the PVS method can be generally used for simulations of spectroscopic properties of solvated molecules and makes multiscale MD/QC computations more affordable. © 2012 Wiley Periodicals, Inc.     

Infrared spectroscopy of N-methylacetamide in water from high-level QM/MM calculations简

The infrared(IR) spectra of the N-methylacetamide molecule in water are calculated by using the MD simulation with high-level QM/MM corrections. The B3LYP and MP2 levels with 6-311++G** basis set are used for the QM region, respectively. Our results show all IR spectra at the B3LYP level are well consistent with the corresponding MP2 results. A dynamical charge fluctuation is observed for each atom along the simulation trajectories due to the electrostatic polarization(EP) effects from surrounding solvent environment. We find that the QM/MM corrected IR spectra satisfactorily reproduce the experimental vibrational features of amide I–III modes.     

Classical and quantum mechanical/molecular mechanical molecular dynamics simulations of alanine dipeptide in water: comparisons with IR and vibrational circular dichroism spectra

We have implemented the combined quantum mechanical (QM)/molecular mechanical (MM) molecular dynamics (MD) simulations of alanine dipeptide in water along with the polarizable and nonpolarizable classical MD simulations with different models of water. For the QM/MM MD simulation, the alanine dipeptide is treated with the AM1 or PM3 approximations and the fluctuating solute dipole moment is calculated by the Mulliken population analysis. For the classical MD simulations, the solute is treated with the polarizable or nonpolarizable AMBER and polarizable CHARMM force fields and water is treated with the TIP3P, TIP4P, or TIP5P model. It is found that the relative populations of right-handed alpha-helix and extended beta and P(II) conformations in the simulation trajectory strongly depend on the simulation method. For the QM/MM MD simulations, the PM3/MM shows that the P(II) conformation is dominant, whereas the AM1/MM predicts that the dominant conformation is alpha(R). Polarizable CHARMM force field gives almost exclusively P(II) conformation and other force fields predict that both alpha-helical and extended (beta and P(II)) conformations are populated with varying extents. Solvation environment around the dipeptide is investigated by examining the radial distribution functions and numbers and lifetimes of hydrogen bonds. Comparing the simulated IR and vibrational circular dichroism spectra with experimental results, we concluded that the dipeptide adopts the P(II) conformation and PM3/MM, AMBER03 with TIP4P water, and AMBER polarizable force fields are acceptable for structure determination of the dipeptide considered in this paper.     

Optical absorption of methoxy and carboethoxy derivatives of 1,3-diphenyl-1H-pyrazolo[3,4-b]quinoline

Paper deals with experimental investigations and quantum chemical calculations of the optical absorption spectra of methoxy and carboethoxy 1,3-diphenyl derivatives of the pyrazoloquinoline ([PQ]): 6-methoxy-1,3-dyphenil-[PQ], 6-methoxy-1,3-(p-methoxyphenyl)-[PQ], 6-methoxy-1-(p-methoxyphenyl)-[PQ] and 6-carboethoxy-1,3-diphenyl-[PQ]. The quantum chemical calculations are performed by means of the semiempirical quantum chemical methods (AM1 or PM3) applied to: (a) the equilibrium molecular conformation in vacuo (T=0 K); (b) the molecular dynamic (MD) trajectory (T=300 K) which includes the dynamics of a certain molecular fragment (moiety) only (fragmental MD simulations); or (c) the MD trajectory obtained for most general case within the total MD simulations at T=300 K. The results of these calculations are compared with the measured spectra of the optical absorption. The quantum chemical simulations show that the dynamics of the methoxy or carboethoxy groups practically does not influence the absorption spectrum whereas the strongest its modification (300相似文献   

Theoretical study of the 1,3-hydrogen shift of triazene in water

The 1,3-hydrogen shift of triazene in aqueous solution was studied with a combination of QM/MM methods. First, the different species involved were characterized and the activation free-energies calculated with ASEP/MD, a method that makes use of the mean field approximation. Then the reaction dynamics was simulated with a QM/MM/MD method. A very strong influence of the solvent was observed, both specific, with the participation of a water molecule, and from the rest of the solvent. The effect of solvation on the geometry and electron distribution of triazene is important: N-N bond lengths tend to be more similar and the molecule acquires a planar structure. For the transition state structure, a substantial degree of ionic nature was found. Dynamic solvent effects were also analyzed.     

Solvent effect on the absorption spectra of coumarin 120 in water: A combined quantum mechanical and molecular mechanical study

The solvent effect on the absorption spectra of coumarin 120 (C120) in water was studied utilizing the combined quantum mechanical∕molecular mechanical (QM∕MM) method. In molecular dynamics (MD) simulation, a new sampling scheme was introduced to provide enough samples for both solute and solvent molecules to obtain the average physical properties of the molecules in solution. We sampled the structure of the solute and solvent molecules separately. First, we executed a QM∕MM MD simulation, where we sampled the solute molecule in solution. Next, we chose random solute structures from this simulation and performed classical MD simulation for each chosen solute structure with its geometry fixed. This new scheme allowed us to sample the solute molecule quantum mechanically and sample many solvent structures classically. Excitation energy calculations using the selected samples were carried out by the generalized multiconfigurational perturbation theory. We succeeded in constructing the absorption spectra and realizing the red shift of the absorption spectra found in polar solvents. To understand the motion of C120 in water, we carried out principal component analysis and found that the motion of the methyl group made the largest contribution and the motion of the amino group the second largest. The solvent effect on the absorption spectrum was studied by decomposing it in two components: the effect from the distortion of the solute molecule and the field effect from the solvent molecules. The solvent effect from the solvent molecules shows large contribution to the solvent shift of the peak of the absorption spectrum, while the solvent effect from the solute molecule shows no contribution. The solvent effect from the solute molecule mainly contributes to the broadening of the absorption spectrum. In the solvent effect, the variation in C-C bond length has the largest contribution on the absorption spectrum from the solute molecule. For the solvent effect on the absorption spectrum from the solvent molecules, the solvent structure around the amino group of C120 plays the key role.     

IR spectra of N-methylacetamide in water predicted by combined quantum mechanical/molecular mechanical molecular dynamics simulations

We applied the combined quantum mechanical (QM)/molecular mechanical (MM) molecular dynamics (MD) simulation method in assessing IR spectra of N-methylacetamide and its deuterated form in aqueous solutions. The model peptide is treated at the Austin Model 1 (AM1) level and the induced dipole effects by the solvent are incorporated in fluctuating solute dipole moments, which are calculated using partial charges from Mulliken population analyses without resorting to any available high-level ab initio dipole moment data. Fourier transform of the solute dipole autocorrelation function produces in silico IR spectra, in which the relative peak intensities and bandwidths of major amide bands are quantitatively compatible with experimental results only when both geometric and electronic polarizations of the peptide by the solvent are dealt with at the same quantum-mechanical level. We cast light on the importance of addressing dynamic charge fluctuations of the solute in calculating IR spectra by comparing classical and QM/MM MD simulation results. We propose the adjustable scaling factors for each amide mode to be directly compared with experimental data.     

The Jahn-Teller effect of the Cr(2+) ion in aqueous solution: Ab initio QM/MM molecular dynamics simulations

The hydration structure of Cr(2+) has been studied using molecular dynamics (MD) simulations including three-body corrections and combined ab initio quantum mechanical/molecular mechanical (QM/MM) MD simulations at the Hartree-Fock level. The structural properties are determined in terms of radial distribution functions, coordination numbers, and several angle distributions. The mean residence time was evaluated for describing ligand exchange processes in the second hydration shell. The Jahn-Teller distorted octahedral [Cr(H(2)O)(6)](2+) complex was pronounced in the QM/MM MD simulation. The first-shell distances of Cr(2+) are in the range of 1.9-2.8 A, which are slightly larger than those observed in the cases of Cu(2+) and Ti(3+). No first-shell water exchange occurred during the simulation time of 35 ps. Several water-exchange processes were observed in the second hydration shell with a mean residence time of 7.3 ps.     

Electronic and optical properties of magnesium phthalocyanine (MgPc) solid films studied by soft X-ray excited optical luminescence and X-ray absorption spectroscopies

In a study to link the optical and structural properties of solid films of magnesium Phthalocyanine (MgPc), a range of synchrotron based spectroscopic methods have been used. These include X-ray excited optical luminescence (XEOL) together with X-ray absorption spectroscopy (XAS) measured both by total electron yield methods (TEY) and by using the optically detected photoluminescence yield method (PLY). XEOL spectra below K shell threshold show a broad emission peak at approximately 860 nm which can be attributed to the optical Q-band of these organic systems, which is then suppressed above the threshold. The shift to higher wavelength compared to optical emission spectra from MgPc in solution is consistent with intermolecular coupling of the excited states in the loosely intermolecular bonded phthalocyanine crystal structure. Zero order total PLY spectra at both C and N K edges are compared to TEY spectra where at the C K edge an inversion of intensity ratios between features is observed. Wavelength-specific PLY absorption spectra taken at 860 nm at the N K edge show a role for sigma* states participating in the luminescence process possibly through the sigma-like lone pair of bridging nitrogen atom, denoted the n --> pi* transition.     

Thermochromism of bithiophenes and internal aromatic chain rotation

The relation between thermochromism and thermal motion of aromatic rings on model bithiophene and 3-butylbithiophene molecules was studied by molecular dynamics (MD) simulations based on semiempirical AM1 hamiltonian. Theoretical optical spectra at various temperatures are generated from the conformations obtained from MD calculations. Alkyl chains have a tendency to tilt bithiophene fragments from co-planarity (connected with blue shift) whereas the unsubstituted systems prefer the higher degree of planarity (connected with red shift) upon the temperature increase. The slope of the linear temperature dependence of the reciprocal maximal wavelengths consists of the above electronic and of the vibrational contribution that (according to Wien’s displacement law) causes always the increase of the above mentioned slope by reciprocal Wien’s constant. This model explains the temperature dependence of experimental UV–vis spectra for dibutylheptathiophene and 3′,3,4′,4-tetrahexylhexathiophene.     

Comparison of basis set effects and the performance of ab initio and DFT methods for probing equilibrium fluctuations

The electronic absorption and emission spectra of large molecules reflect the extent and timescale of electron-vibration coupling and therefore the extent and timescale of relaxation/reorganization in response to a perturbation. In this paper, we present a comparison of the calculated absorption and emission spectra of NADH in liver alcohol dehydrogenase (LADH), using quantum mechanical/molecular mechanical methods, in which we vary the QM component. Specifically, we have looked at the influence of basis set (STO-3G, 3-21G*, 6-31G*, CC-pVDZ, and 6-311G**), as well as the influence of applying the DFT TD-B3LYP and ab initio TD-HF and CIS methods to the calculation of absorption/emission spectra and the reorganization energy (Stokes shift). The ab initio TD-HF and CIS methods reproduce the experimentally determined Stokes shift and spectral profiles to a high level of agreement, while the TD-B3LYP method significantly underestimates the Stokes shift, by 45%. We comment on the origin of this problem and suggest that ab initio methods may be naturally more suited to predicting molecular behavior away from equilibrium geometries.     

The implementation of a fast and accurate QM/MM potential method in Amber

Version 9 of the Amber simulation programs includes a new semi-empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many nanoseconds. The link atom approach used for treating the QM/MM boundary shows improved performance, and the user interface has been rewritten to bring the format into line with classical MD simulations. Support is provided for the PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi-empirical Hamiltonians as well as the self-consistent charge density functional tight binding (SCC-DFTB) method. Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation.     

Effect of pressure on the vibrational structure of insensitive energetic material 5-nitro-2,4-dihydro-1,2,4-triazole-3-one

The Raman spectra of alpha form 5-nitro-2,4-dihydro-1,2,4-triazole-3-one (alpha-NTO, space group P) were measured in a high-pressure vessel diamond anvil cell (DAC). The pressure was increased to 27.6 GPa. In general, Raman bands show a blue shift because of the nature of the molecule packing as a high-pressure effect, but some particular bands exhibited a red shift, disappearance, split, or slight shifting in our experiments. Those red-shifting bands concerning hydrogen bonds, i.e., carbonyl and amino groups, are likely to work as a stabilizer against stimuli to the molecule or crystal. This stabilizing nature might characterize the insensitivity of NTO. Molecular dynamic (MD) calculations were performed to reveal the high-pressure effect of the alpha-NTO crystal. The coordinates of individual atoms in the crystal structure were obtained using X-ray diffraction analysis. The pressure dependence of the power spectra of the correlation functions of the C=O bond length in NTO was calculated. A unique high-pressure effect of the alpha-NTO crystal was found on the power spectra. The peak frequency in the power spectrum of the C=O stretching vibration exhibited a red shift with an increase in pressure to 10.0 GPa, while the peak intensity considerably decreased under the same pressure process, because this bond length increased with an increase in pressure to 10.0 GPa. At a pressure of >20.0 GPa, a blue shift appeared. These results of the MD calculations are in good agreement with our experimental data.     

Ba1－xSrxTiO3的Sol-gel法制备与结构相变研究

采用sol-gel法制备了钛酸锶钡(Ba1－xSrxTiO3)．用XRD、DSC、Raman等表征技术研究了Ba1－xSrxTiO3的晶体结构和相变行为.结果表明,随着锶含量的增加,晶胞体积逐渐减小,c/a趋近于1,相变温度降低,相变热减少,相变弥散性增强,且存在热滞现象.Raman光谱发生有趣变化,当x=0.30时,室温下发生结构相变, Ba1－xSrxTiO3以立方相为主要存在相,相变具有有序-无序特征.     

Experimental and theoretical investigation of the first overtone spectrum of 1,3,5-trinitrotoluene

Vibrational overtone spectroscopy is a powerful tool for studying intramolecular and intermolecular interactions. We report on a combined experimental and modeling study of the C-H stretch first overtone of bulk 1,3,5-trinitrotoluene (TNT) and TNT on fumed-silica powder. We recorded the overtone spectra by laser photoacoustic spectroscopy and compared them with those predicted with the harmonically coupled anharmonic oscillator model in the 5600-6600 cm(-1) region. The model systems included single molecules and hybrid quantum and molecular mechanical (QM:MM) clusters to account for the effects of intermolecular interactions on the observed spectra. We performed the hybrid QM:MM calculations at the HF/6-31+G(d,p), B3LYP/6-31+G(d,p), and MP2/6-31+G(d,p) levels of theory and with the universal force field (UFF) to account for van der Waals and electrostatic effects from surrounding molecules. Overtone spectra calculated from the MP2 level of theory, using a HF/3-21+G* calculation to assign molecular charges in the MM layer, and the Merz-Singh-Kollman population analysis for assigning partial charge in the QM layer and determining the transition dipole moment agreed best with the experimental data.