Nudged elastic stiffness band method: A method to solve kinks problems of reaction paths.

The nudged elastic band (NEB) method has been widely employed for reaction path (RP) finding; however, certain NEB calculations do not converge to the minimum energy paths (MEPs) because of the occurrence of kinks, which are caused by the free bending of bands. Thus, we propose an extension of the NEB method, called the nudged elastic stiffness band (NESB) method, which adds the stress of stiffness using a beam theory. Here we present results from three examples: the NFK potential, the RPs of the Witting reaction, and finding saddle points for a set of five chemical reaction benchmarks. The results showed that the NESB method has three advantages: to decrease the number of iterations, shrink the length of the pathways from reducing unnecessary fluctuations, and find TS structures by converging to paths close to the MEPs for systems that have sharp curves on the MEPs.

Curvature-weighted nudged elastic band method using the Riemann curvature.

The nudged elastic band (NEB) method is utilized to find reaction paths (RPs) using discretized intermediate structures called "images" between a reactant and a product. In fact, NEB calculations do not always converge because of the bent of RPs. Mathematically, more images are needed for complex curves, and here, we focused on the curvature. In this study, we propose a new method for calculating the curvature of the RPs as well as a method for weighting the spring constant of the NEB with the curvature, which we named the curvature weighted NEB (CW-NEB) method. In addition, we will propose the CW-NEB method with the climbing image (CI) method (CW-CI-NEB). To show the efficiency of our method, calculations for the ene-reaction of the CW-CI-NEB method were performed and compared with those of the CI-NEB methods. The CW-CI-NEB methods converged in shorter iteration times than the CI-NEB calculation, which was found by gathering the bent of RPs.

Calculation of the permeability coefficients of small molecules through lipid bilayers by free-energy reaction network analysis following the explicit treatment of the internal conformation of the solute.

Biomembrane permeation represents a major barrier to pharmacokinetics. During preclinical drug discovery, the coefficients of the permeation of molecules through lipid bilayers account for a valuable property of such molecules. Therefore, the control of the permeation of molecules through lipid bilayers is an essential factor in drug design, and the estimation of the permeation phenomena is a crucial study in pharmacy. Thus, there are many published studies on the theoretical estimations of permeation coefficients. Here, we propose a molecular dynamics (MD) simulation method for estimating the permeation of small molecules through lipid bilayers based on the free-energy reaction network (FERN) analysis. In this method, the collective variables (CVs) of the free energy calculations explicitly include the conformational changes in the rotational bonds of the solute molecules. The advantages of the present method over the other method are that it is possible to estimate reaction pathways and their reaction rates, i.e., permeation coefficients or passage times, in multidimensional space spanned by CVs though conventional methods such as the umbrella sampling method and target MDs often dealt with a few degrees of freedom. To demonstrate the efficacy of our method, we calculate the coefficients of the permeation of three small aromatic peptides, namely N-acetylphenylalanineamide (Ac-Phe-NH2 or NAFA), N-acetyltyrosineamide (Ac-Tyr-NH2 or NAYA), and N-acetyltryptophanamide (Ac-Trp-NH2 or NATA), through a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayer. In these cases we adopted one CV for the permeation direction and four CVs for the internal rotational coordinates. The results reveal that the permeation coefficients of NAFA, NAYA, and NATA are 1.7 × 10-2, 0.51 × 10-4, and 5.7 × 10-4 cm s-1, respectively. Compared with the experimental data, our simulation results followed the same trend, i.e., NAFA > NATA > NAYA. By analyzing the structures of metastable points of the solute molecules, our simulation result reveals that the aforementioned trend is caused by the differences in stability among their rotamers. Furthermore, we evaluate the statistical fluctuation of the rotamers, and the time scale of flipping the side chain reveals that the structures rigidify as the ligand moves deeper into the membrane.

Theoretical Design of Blue-Color Phosphorescent Complexes for Organic Light-Emitting Diodes: Emission Intensities and Nonradiative Transition Rate Constants in Ir(ppy)2(acac) Derivatives.

Theoretical calculations of phosphorescent spectra and nonradiative transition (NRT) rate constants for S1 ⇝ T1, T1 ⇝ S0, and S1 ⇝ S0 were carried out to determine the best candidate for a blue-color phosphorescent complex among several derivatives of bis(2-phenylpyridine)(acetylacetonate)iridium(III). The geometries of the ground state (S0), the lowest triplet state (T1), and the lowest excited singlet state (S1) were optimized at the levels of density functional theory, in which B3LYP functionals and SBKJC+p basis sets were used. The NRT rate constants were derived by using a generating function method within the displaced harmonic oscillator model. The results of the calculation for phosphorescence showed that the introduction of F and/or CN substituents at the 4'/6'-th and 5'-th sites in 2-phenylpyridinate (ppy) ligands, respectively, causes a blue shift of the emission spectra. They also suggest that Ir(5-CN,6-F-ppy)2(acac), denoted 3(56) in the text, is a good candidate for a blue-color phosphorescent complex because a blue shift of emission spectra and a moderate intensity are obtained for phosphorescence and, furthermore, this complex is calculated to have a large rate constant for S1 ⇝ T1 and relatively smaller rate constants for T1 ⇝ S0 and S1 ⇝ S0 based on the calculations of spin-orbit coupling and nonadiabatic coupling constants.

Exploring the Reaction Paths on the Potential Energy Surfaces of the S1 and T1 States in Methylenecyclopropane.

The reaction paths of methylenecyclopropane 1 on the potential energy surfaces (PESs) of the lowest triplet (T1 ) state and the lowest excited singlet (S1 ) state, as well as that of the ground state (S0 ), were explored by using the nudged elastic band method at the MRMP2//MCSCF/6-31++G(d,p) and DFT(B3LYP)/6-31++G(d,p) levels of theory. After vertical excitation of 1, three transition states on the PES of the lowest triplet state and one transition state on the S1 PES were found along the reaction path to produce a carbene, cyclobutylidene 2. All of these transition states are lower in energy than the S1 state produced by vertical excitation at the S0 energy minimum in 1. Fast transition is predicted to occur from the T1 state or from the S1 state to the S0 state due to strong spin-orbit coupling or nonadiabatic coupling in the geometrical vicinity of 2. On the MRMP2 S0 PES, the energy barriers of 5.0, 10.3 and 13.5 kcal mol-1 were obtained for C migration reaction (backward reaction), 1,2-H migration reaction to cyclobutene 3, and 1,3-H migration reaction to bicyclopropane 4, respectively, started at 2. The introduction of phenyl groups makes the energy barriers smaller due to the π conjugation between the carbene center and phenyl groups.

Theoretical Examination of the Plausible Reaction Process for Stereoselective Synthesis of Hexapole Helicene via a Palladium-Catalyzed [2 + 2 + 2] Cyclotrimerization of [5]Helicenyl Aryne.

The reaction mechanisms of the plausible reaction process for the synthesis of hexapole helicene via a palladium-catalyzed [2 + 2 + 2] cyclotrimerization of [5]helicenyl aryne were examined using a theoretical approach. In a previous experimental study, this reaction selectively produced C2-symmetrical hexapole helicene, even though the D3-symmetrical structure is thermodynamically more stable. To clarify the mechanism underlying this reaction, density functional theory (DFT) and transition-state-theory calculations were used to evaluate the reaction profile and kinetic rate constants of the primary reactions. The thus obtained results suggest that the first step of the [2 + 2 + 2] cyclotrimerization is not a Diels-Alder reaction but an insertion of the helicenyl aryne into a metallacyclopentadiene. Subsequently, we clarified that the formation of the D3-symmetrical product is precluded by the high free-energy barrier of this reaction, while the C2-symmetrical product can be obtained at 300 K. Simulations of the time evolution of the molar fractions of the isomers were carried out based on the evaluated kinetic rate constants. The experimental result that the C2-symmetrical product is formed predominantly at 300 K was successfully reproduced in the simulations, while the isomerization into the more stable D3 hexapole helicene structure is predicted to occur at 400 K.

Spin-Orbit Coupling Constants in Atoms and Ions of Transition Elements: Comparison of Effective Core Potentials, Model Core Potentials, and All-Electron Methods.

The spin-orbit coupling constants (SOCC) in atoms and ions of the first- through third-row transition elements were calculated for the low-lying atomic states whose main electron configuration is [ nd] q ( q = 1-4 and 6-9, n = the principal quantum number), using four different approaches: (1) a nonrelativistic Hamiltonian used to construct multiconfiguration self-consistent field (MCSCF) wave functions utilizing effective core potentials and their associated basis sets within the framework of second-order configuration interaction (SOCI) to calculate spin-orbit couplings (SOC) using one-electron Breit-Pauli Hamiltonian (BPH), (2) a nonrelativistic Hamiltonian used to construct MCSCF wave functions utilizing model core potentials and their associated basis sets within the framework of SOCI to calculate SOC using the full BPH, (3) nonrelativistic and spin-independent relativistic Hamiltonians used to construct MCSCF wave functions utilizing all-electron (AE) basis sets within the framework of SOCI to calculate SOC using the full BPH, and (4) a relativistic Hamiltonian given by the exact two-component (X2C) transformation for construction of Kramers-restricted relativistic configuration interaction wave functions. In this investigation, these four approaches are referred to as ECP, MCP, AE, and X2C methods, respectively. The ECP, MCP, and AE methods are so-called two-step approaches (TSA), while the X2C method is a one-step approach (OSA). In the AE method, three different calculations-relativistic elimination of small components (RESC), third-order Douglas-Kroll-Hess (DKH3), and infinite-order two-component (IOTC) relativistic correction-were performed for the estimation of the scalar relativistic components in addition to those of the nonscalar relativistic (NSR) contributions. The calculated SOCC are compared to the available experimental data via the Landé interval rule. Although there are several exceptions, including states whose main configuration is [ nd]5, the average differences between the ECP and AE (IOTC) SOCC and between the ECP and the X2C SOCC are mostly less than 20%. The differences between the ECP and the experimental SOCC are even smaller. No serious discrepancy was found between the TSA and OSA predictions of SOCC for the first- and second-row transition elements in comparison to experiment. For atoms and ions of the third-row transition elements, the SOCC calculated through the Landé interval rule are not reliable. The low-energy spin-mixed (SM) states originating from a [5d] q configuration ( q = 2-4) have a larger energy lowering due to the SOC effects, in comparison with those for atoms and ions of the first- and second-row transition elements. For the spin-mixed (SM) states originating from a [5d] q configuration ( q = 6-8), the energy lowering of all 4F7/2, 5D1, and 5D3 states due to the SOC effects is smaller than those of the other SM states. This difficulty, which also arises for the MCP, AE, and X2C (OSA) approaches, suggests that the LS-coupling scheme is inappropriate.

Numerical Estimation of the Pseudo-Jahn-Teller Effect Using Nonadiabatic Coupling Integrals in Monocyclic and Bicyclic Conjugated Molecules.

The pseudo-Jahn-Teller (pJT) effect in monocyclic and bicyclic conjugated molecules was investigated by using the state-averaged multiconfiguration self-consistent field (MCSCF) method, together with the 6-31G(d,p) basis sets. Following the perturbation theory, the force constant along a normal mode Q is given by the sum of the classical force constant and the vibronic contribution (VC) resulting from the interaction of the ground state with excited states. The latter is given as the sum of individual contributions arising from vibronic interactions between the ground state and excited states. In the present work, each VC was calculated on the basis of nonadiabatic coupling (NAC) integrals. Furthermore, the classical force constant was estimated by taking advantage of the VC and the force constant obtained by vibrational analyses. For pentalene and heptalene, the present method seems to overestimate the VC in absolute value because of the small energy gap between the ground state and the lowest excited state. However, we are confident that the VC and the classical force constant for the other molecules are reasonable in magnitude in comparison with available literature information. Thus, it is proved that the present method is applicable and useful for numerical estimation of pJT effect.

Free Energy Contribution Analysis Using Response Kernel Approximation: Insights into the Acylation Reaction of a Beta-Lactamase.

A widely applicable free energy contribution analysis (FECA) method based on the quantum mechanical/molecular mechanical (QM/MM) approximation using response kernel approaches has been proposed to investigate the influences of environmental residues and/or atoms in the QM region on the free energy profile. This method can evaluate atomic contributions to the free energy along the reaction path including polarization effects on the QM region within a dramatically reduced computational time. The rate-limiting step in the deactivation of the ß-lactam antibiotic cefalotin (CLS) by ß-lactamase was studied using this method. The experimentally observed activation barrier was successfully reproduced by free energy perturbation calculations along the optimized reaction path that involved activation by the carboxylate moiety in CLS. It was found that the free energy profile in the QM region was slightly higher than the isolated energy and that two residues, Lys67 and Lys315, as well as water molecules deeply influenced the QM atoms associated with the bond alternation reaction in the acyl-enzyme intermediate. These facts suggested that the surrounding residues are favorable for the reactant complex and prevent the intermediate from being too stabilized to proceed to the following deacylation reaction. We have demonstrated that the free energy contribution analysis should be a useful method to investigate enzyme catalysis and to facilitate intelligent molecular design.

Amorphous Solid Simulation and Trial Fabrication of the Organic Field-Effect Transistor of Tetrathienonaphthalenes Prepared by Using Microflow Photochemical Reactions: A Theoretical Calculation-Inspired Investigation.

The p-type organic semiconductor (OSC) material tetrathieno[2,3-a:3',2'-c:2″,3″-f:3‴,2‴-h]naphthalene (2TTN) and its alkyl-substituted derivatives C(n)-2TTNs (n = 6, 8, and 10) have been developed based on the results of theoretical calculation-inspired investigation. A hole mobility for amorphous C(n)-2TTNs (10(-2)-10(-3) cm(2) V(-1) s(-1)) was accurately predicted by using a novel statistical method in which the geometric mean of the mobilities for many individual small molecular flocks in an amorphous solid was obtained by using molecular mechanical molecular dynamics simulations and quantum chemical calculations. The simulation also suggests that upon increasing the length of alkyl chains in C(n)-2TTNs the mobilities become smaller as a consequence of a decrease in transfer integral values. C(n)-2TTNs are synthesized in a microflow reactor through photoreactions of the corresponding precursors. C(n)-2TTNs are then utilized in the fabrication of organic field-effect transistors (OFETs). Although spin-coated thin films of C(n)-2TTNs are crystalline, the hole mobilities (10(-2)-10(-3) cm(2) V(-1) s(-1)) of trial OFETs decrease upon elongation of the alkyl chains. This finding parallels the results of theoretical simulation. The simulation method for amorphous solids developed in this effort should become a useful tool in studies aimed at designing new OSC materials.

Efficient approach to include molecular polarizations using charge and atom dipole response kernels to calculate free energy gradients in the QM/MM scheme.

An efficient approach to evaluate free energy gradients (FEGs) within the quantum mechanical/molecular mechanical (QM/MM) framework has been proposed to clarify reaction processes on the free energy surface (FES) in molecular assemblies. The method is based on response kernel approximations denoted as the charge and the atom dipole response kernel (CDRK) model that include explicitly induced atom dipoles. The CDRK model was able to reproduce polarization effects for both electrostatic interactions between QM and MM regions and internal energies in the QM region obtained by conventional QM/MM methods. In contrast to charge response kernel (CRK) models, CDRK models could be applied to various kinds of molecules, even linear or planer molecules, without using imaginary interaction sites. Use of the CDRK model enabled us to obtain FEGs on QM atoms in significantly reduced computational time. It was also clearly demonstrated that the time development of QM forces of the solvated propylene carbonate radical cation (PC˙(+)) provided reliable results for 1 ns molecular dynamics (MD) simulation, which were quantitatively in good agreement with expensive QM/MM results. Using FEG and nudged elastic band (NEB) methods, we found two optimized reaction paths on the FES for decomposition reactions to generate CO2 molecules from PC˙(+), whose reaction is known as one of the degradation mechanisms in the lithium-ion battery. Two of these reactions proceed through an identical intermediate structure whose molecular dipole moment is larger than that of the reactant to be stabilized in the solvent, which has a high relative dielectric constant. Thus, in order to prevent decomposition reactions, PC˙(+) should be modified to have a smaller dipole moment along two reaction paths.

Synthesis of a double helicene by a palladium-catalyzed cross-coupling reaction: structure and physical properties.

For this study, twisted π-extended helicene 1 and double helicene 2 with a helicene framework were synthesized through palladium-catalyzed C-H arylation or Suzuki-Miyaura coupling reaction. X-ray crystallography revealed grossly twisted structures that were soluble in various conventional organic solvents. Optical properties based on UV/Vis and fluorescence spectra were measured. Electrochemical properties were also studied by measurements of cyclic voltammetry in 1 and 2, which revealed their HOMO and the LUMO energies. Theoretical calculation supports their HOMO and LUMO energies and molecular orbitals. Furthermore, a racemization process of 2 predicted that the activation free energy at 300 K would be 31.8 kcal mol(-1) by DFT calculation, which indicated the static helicity at 300 K.

Theoretical investigation of the reaction mechanism of ClONO2 + HCl → HNO3 + Cl2 on (H2O)n (n = 0-3) cluster.

Hydrated chlorine nitrate and hydrogen chloride ClONO2·HCl·(H2O)n (n = 0-3) clusters were investigated by using the MP2/aug-cc-pVTZ level of theory to clarify the reaction mechanism of Cl2 production. Isomeric stable structures found in n = 2 and 3 clusters have equivalent binding energies and the reaction barrier drastically decreases to be 2.1 kcal/mol at n = 3. The plausible reaction pathways were proposed according to calculated structures and energies, where the zero-point-energy corrections are important to determine the energy profiles of reactions especially for the n = 3 cluster. The kinetic analysis using the transition state theory suggested that the reaction rate constant from the original reactants to the product of n = 3 is 1.8 × 10(5) times larger than that of n = 2 cluster. Even though the small amount of the molar concentration of HCl(H2O)3 is obtained, the overall reaction rate of the trihydrate reaction is still 35 times faster than that of the dihydrate.

Toward a new approach for determination of solute's charge distribution to analyze interatomic electrostatic interactions in quantum mechanical/molecular mechanical simulations.

We present an alternative approach to determine "density-dependent property"-derived charges for molecules in the condensed phase. In the case of a solution, it is essential to take into consideration the electron polarization of molecules in the active site of this system. The solute and solvent molecules in this site have to be described by a quantum mechanical technique and the others are allowed to be treated by a molecular mechanical method (QM/MM scheme). For calculations based on this scheme, using the forces and interaction energy as density-dependent property our charges from interaction energy and forces (CHIEF) approach can provide the atom-centered charges on the solute atoms. These charges reproduce well the electrostatic potentials around the solvent molecules and present properly the picture of the electron density of the QM subsystem in the solution system. Thus, the CHIEF charges can be considered as the atomic charges under the conditions of the QM/MM simulation, and then enable one to analyze electrostatic interactions between atoms in the QM and MM regions. This approach would give a view of the QM nuclei and electrons different from the conventional methods.

Ab initio electron correlated studies on the intracluster reaction of NO+ (H2O)(n) → H3O+ (H2O)(n-2) (HONO) (n = 4 and 5).

Hydrated nitrosonium ion clusters NO(+)(H(2)O)(n) (n = 4 and 5) were investigated by using MP2/aug-cc-pVTZ level of theory to clarify isomeric reaction pathways for formation of HONO and fully hydrated hydride ions. We found some new isomers and transition state structures in each hydration number, whose lowest activation energies of the intracluster reactions were found to be 4.1 and 3.4 kcal mol(-1) for n = 4 and n = 5, respectively. These thermodynamic properties and full quantum mechanical molecular dynamics simulation suggest that product isomers with HONO and fully hydrated hydride ions can be obtained at n = 4 and n = 5 in terms of excess hydration binding energies which can overcome these activation barriers.

A minimal implementation of the AMBER-GAUSSIAN interface for ab initio QM/MM-MD simulation.

For applying to a number of theoretical methodologies based on an ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics method connecting AMBER9 with GAUSSIAN03, we have developed an AMBER-GAUSSIAN interface (AG-IF), which can be one of the simplest architectures. In the AG-IF, only a few subroutines addition is necessary to retrieve the QM/MM energy and forces, obtained by GAUSSIAN, for solving a set of Newtonian equations of motion in AMBER. It is, therefore, easy to be modified for individual applications since AG-IF utilizes most of those functions originally equipped not only in AMBER but also in GAUSSIAN. In the present minimal implementation, only AMBER is modified, whereas GAUSSIAN is left unchanged. Moreover, a different method of calculating electrostatic forces of MM atoms interacting with QM region is proposed. Using the AG-IF, we also demonstrate three examples of application: (i) the QM versus MM comparison in the radial distribution function, (ii) the free energy gradient method, and (iii) the charge from interaction energy and forces.

Tetrahydrides of third-row transition elements: spin-orbit coupling effects on the stability of rhenium tetrahydride.

The potential energy surfaces of low-lying states in rhenium tetrahydride (ReH(4)) were explored by using the multiconfiguration self-consistent field (MCSCF) method together with the SBKJC effective core potentials and the associated basis sets augmented by a set of f functions on rhenium atom and by a set of p functions on hydrogen atoms, followed by spin-orbit coupling (SOC) calculations to incorporate nonscalar relativistic effects. The most stable structure of ReH(4) was found to have a D(2d) symmetry and its ground state is (4)A(2). It is found that this is lower in energy than the dissociation limit, ReH(2)+H(2), after dynamic correlation effects are taken into account by using second-order multireference Møller-Plesset perturbation (MRMP2) calculations. This reasonably agrees with previous results reported by Andrews et al. [J. Phys. Chem. 107, 4081 (2003)]. The present investigation further revealed that the dissociation reaction of ReH(4) cannot occur without electronic transition from the lowest quartet state to the lowest sextet state. This spin-forbidden transition can easily occur because of large SOC effects among low-lying states in such heavy metal-containing compounds. The minimum-energy crossing (MEX) point between the lowest quartet and sextet states is proved to be energetically and geometrically close to the transition state for the dissociation reaction on the potential energy surface of the lowest spin-mixed state. The MEX point (C(2) symmetry) was estimated to be 9184 cm(-1) (26.3 kcal/mol) higher than the (4)A(2) state in D(2d) symmetry at the MRMP2 level of theory. After inclusion of SOC effects, an energy maximum on the lowest spin-mixed state appears near the MEX point and is recognized as the transition state for the dissociation reaction to ReH(2)+H(2). The energy barrier for the dissociation, evaluated to be MEX in the adiabatic picture, was calculated to be 5643 cm(-1) (16.1 kcal/mol) on the lowest spin-mixed state when SOC effects were estimated at the MCSCF level of theory.

Spin-orbit coupling effects in dihydrides of third-row transition elements. II. Interplay of nonadiabatic coupling in the dissociation path of rhenium dihydride.

This is the second paper in a series of investigations on spin-orbit coupling (SOC) effects in dihydrides of third-row transition elements. The dissociation path of rhenium dihydride was explored using the multiconfiguration self-consistent-field method followed by diagonalization of SOC matrices, in which the Stevens-Basch-Krauss-Jasien-Cundari (SBKJC) basis sets were employed after adding one set of polarization functions for each atom. The most stable rhenium dihydride has a linear structure and its ground state is (6)Sigma(g)(+). Both C(2v) and C(s) dissociation paths into a Re atom and a hydrogen molecule (Re((6)S) + H(2)((1)Sigma(g)(+))) were explored on the potential energy curves of low-lying states. A relatively high energy barrier was obtained along the C(2v) path and two conical intersections were found at the H-Re-H angles of 29.8 degrees and 96.1 degrees along the C(2v) path. Since it was revealed that the geometrical deformation to C(s) symmetry at the H-Re-H angle of 29.8 degrees does not provide explicit lowering of the energy barrier for the dissociation, even after considering nonadiabatic couplings (NACs) in the neighborhood of the conical intersections, it can be concluded that the most feasible path is hopping from the lowest (6)A(1) state to the lowest (6)B(2) state at the H-Re-H angle of 96.1 degrees followed by hopping from the lowest (6)B(2) state back to the lowest (6)A(1) state at the H-Re-H angle of 29.8 degrees, where the latter crossing point is the highest in energy along this path. Thus, when the molecular system can reach the areas of these crossing points, the molecular system hops from one of the states to another owing to NAC or SOC effects; especially, SOC effects become important at the crossing point with C(2v) symmetry.

Molecular dynamics simulation study on stabilities and reactivities of NADH cytochrome B5 reductase.

Binding free energies between coenzyme (FAD and NADH) and the apoenzyme of NADH-cytochrome b5 reductase (b5R) were estimated by applying the continuum Poisson-Boltzmann (PB) model to structures sampled from molecular dynamics simulations in explicit water molecules. Important residues for the enzymatic catalysis were clarified using a computational alanine scanning method. The binding free energies calculated by applying an alanine scanning method can successfully reproduce the trends of the measured steady-state enzymatic activities kcatNADH/KmNADH. Significant decreases in the binding free energy are expected when one of the four residues Arg91, Lys110, Ser127, and Thr181 is mutated into Ala. According to the results of the molecular dynamics simulation, Thr181 is considered to be one of the key residues that helps NADH to approach the isoalloxazine in FAD. Finally, we have constructed very simplified model systems and carried out density functional theory calculations using B3LYP/LANL2DZ//ROHF(or RHF)/LANL2DZ level of theory in order to elucidate a realistic and feasible mechanism of the hydride-ion transfer from NADH to FAD affected by HEME(Fe3+) as an electron acceptor. Our calculated results suggest that the electron and/or hydride-ion transfer reaction from NADH to FAD can be accelerated in the presence of HEME(Fe3+).

Magnetic resonance imaging and magnetic resonance myelography in the presurgical diagnosis of lumbar foraminal stenosis.

STUDY DESIGN: Retrospective case series with a control group. OBJECTIVE: To measure the diagnostic performance of magnetic resonance imaging (MRI) and MR myelography (MRM) for symptomatic foraminal stenosis in patients who need surgery. SUMMARY OF BACKGROUND DATA: MR images are extensively used in the evaluation of foraminal stenosis and are often used to evaluate nerves exiting from the foramen. There has been no published report of the diagnostic performance of these imaging methods (MRI and MRM). METHODS: Diagnostic performances were studied in 90 patients in whom the site of the stenosis was confirmed by means of selective decompression surgeries. The disease prevalence among patients was 26% (23 of 90 patients). The disease prevalence among foramens was 3% (25 of 936 foramens). The prevalence of abnormal findings in 27 asymptomatic volunteers was also studied. Two blinded observers interpreted foraminal narrowing on combinations of sagittal and axial MR images, abnormalities of the course of the nerve root in the foramen, and spinal nerve swelling on MRM. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for the diagnosis of symptomatic foraminal stenosis were 96%, 67%, 4%, and 100%, respectively. The corresponding values for abnormal nerve root course on MRM were 96%, 83%, 7%, and 100%, respectively, and for spinal nerve swelling on MRM were 60%, 99%, 35%, and 99%, respectively. CONCLUSIONS: Compared with conventional MRI, MRM affords more specific information for the presurgical diagnosis of symptomatic foraminal stenosis.