Dayle M. A. Smith

AB INITIO THEORETICAL STUDY OF DIPOLE-BOUND ANIONS OF MOLECULAR COMPLEXES : WATER TETRAMER ANIONS

We present results of ab initio calculations of the (H2O)4/(H2O)4− system. The main conclusions of this work are as follows: The calculated results predict that water tetramer anions are metastable systems in agreement with weak spectral manifestation of these systems in gas-phase experiments of Bowen and co-workers; the excess electrons in all four structural isomers of water tetramer anions found in the calculations are attached to the clusters by the virtue of dipole-electron interaction; all four (H2O)4− anions found in the calculations are almost isoenergetic but have different vertical electron detachment energies (VDEs) ranging from 22 to 279 meV; the most stable cyclic structure of (H2O)4 has a null dipole moment and does not form a dipole–bound state with an excess electron; the water tetramer anions observed experimentally probably are formed as a result of hydration of the water dimer anion, (H2O)2−, by a neutral water dimer or by hydration of the water trimer anion, (H2O)3−, by a single water ...

Experimental and ab initio theoretical studies of electron binding to formamide, N-methylformamide, and N,N-dimethylformamide

The influence of methylation upon adiabatic electron affinities of formamide (F), N- methylformamide (NMF), and N,N-dimethylformamide (DMF) is experimentally investigated by means of Rydberg electron transfer spectroscopy and calculated with the use of high-level ab initio methods. In the anions of these systems the excess electrons are captured in diffuse dipole-bound states. The methylation of formamide results in a slight increase of the dipole moment and in an increased molecular size. The two factors have opposite effects on the electron affinity. Both experimental data and theoretical results are in agreement, showing that the molecular size effect dominates and that the electron affinity noticeably decreases with the methylation.

The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

A radical route to making methane Microorganisms are the main drivers of Earths methane cycle. The enzyme ultimately responsible for biological methane production has an ambiguous mechanism because it involves difficult-to-isolate reaction intermediates. Wongnate et al. used stopped-flow and rapid freeze-quench experiments to trap a methyl radical in the active site of methyl-coenzyme M reductase (see the Perspective by Lawton and Rosenzweig). Spectroscopy demonstrated that cofactor F430 contained Ni(II), consistent with computational results. The final step of methanogenesis thus proceeds through Ni(II)-thiolate and methyl radical intermediates rather than an organometallic methyl-Ni(III) mechanism. Science, this issue p. 953;, see also p. 892 The final step of methanogenesis proceeds via Ni(II)-thiolate and methyl radical intermediates. Methyl-coenzyme M reductase, the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the biological production of more than 1 billion tons of methane per year. The mechanism of methane synthesis is thought to involve either methyl-nickel(III) or methyl radical/Ni(II)-thiolate intermediates. We employed transient kinetic, spectroscopic, and computational approaches to study the reaction between the active Ni(I) enzyme and substrates. Consistent with the methyl radical–based mechanism, there was no evidence for a methyl-Ni(III) species; furthermore, magnetic circular dichroism spectroscopy identified the Ni(II)-thiolate intermediate. Temperature-dependent transient kinetics also closely matched density functional theory predictions of the methyl radical mechanism. Identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas.

Experimental and theoretical ab initio study of the influence of N-methylation on the dipole-bound electron affinities of thymine and uracil

The influence of N-methylation on the dipole-bound electron affinities of pyrimidine nucleic acid bases, uracil and thymine, has been investigated theoretically using ab initio quantum mechanical calculations, and experimentally using Rydberg electron transfer spectroscopy. Both experiment and theory are consistent in showing that replacement of hydrogen atoms by methyl groups reduces electron affinities corresponding to formation of dipole-bound anions of these systems. Also, the distortion of the anion geometries with respect to the geometries of the neutral parents are reduced with the methylation.

Structures and electron affinities of indole–(water)N clusters

Rydberg electron transfer spectroscopy (RET) has been used to determine the dipole-bound electron affinity of the indole molecule, and the value of 3 meV was obtained. RET has also been employed to study [indole–(water)N]− cluster anions and the results have been interpreted with the help of ab initio calculations. It has been shown that for N=1 and 2 only dipole-bound anions are formed and that the electron attachment induces large amplitude motions in these systems. [Indole–(water)N]− anions with N=3 and 4 have not been observed. This finding for N=3 is consistent with a low theoretically predicted dipole moment of the neutral indole–(water)3 complex, which is insufficient for the formation of a stable dipole-bound anion. Above N=5, RET experiments showed formation of valence [indole–(water)N]− anions. From the observed size threshold for the formation of these anions, the negative value of the valence electron affinity of indole equal to −1.03±0.05 meV was deduced.

Multiplet splittings and other properties from density functional theory: an assessment in iron–porphyrin systems

In transition metal compounds with spin states close in energy, the magnitude and sign of the energy splitting calculated with density functional theory depends strongly on the functional used. Therefore we must turn to additional criteria to assess the level of accuracy and reliability of predictions based on this level of theory. We report optimized geometries, total energies, and Mössbauer quadrupole splitting values for low-spin and high-spin, ferric and ferrous model hemes using a variety of gradient-corrected and hybrid functionals. In one model, the iron–porphyrin is axially ligated by two strong-field imidazole ligands [FeP(Im)2] and has a low-spin ground state. In the other model complex the axial ligands are two weak-field, water molecules [FeP(H2O)2], and have a high-spin ground state. Among all the functionals used (UHF, B3LYP, B3LYP*, BLYP, half-and-half, LSDA), the B3LYP hybrid functional most consistently reproduced the experimental geometry, Mössbauer, and spin state data for the two model hemes. Simply gradient-corrected functionals exhibit strong biases towards low spin states, while Hartree–Fock favours strongly high spin states. These findings suggest that for systems with similar characteristics of several accessible electronic spin configurations, it is imperative to include properties other than just the energy in the assessment of the DFT predictions.

Ab initio theoretical study of dipole-bound anions of molecular complexes: (HF)3− and (HF)4− anions

Ab initio calculations have been performed to determine structures and vertical electron detachment energy (VDE) of the hydrogen fluoride trimer and tetramer anions, (HF)3− and (HF)4−. In these systems the excess electron is bound by the dipole field of the complex. It was determined that, unlike the neutral complexes which prefer the cyclic structures, the equilibrium geometries of the anions have “zig–zag” shapes. For both complexes the predicted VDEs are positive [210 meV and 363 meV for (HF)3− and (HF)4−, respectively], indicating that the anions are stable systems with respect to the vertical electron detachment. These results were obtained at the coupled-cluster level of theory with single, double and triple excitations [CCSD(T) method; the triple-excitation contribution in this method is calculated approximately using the perturbation approach] with the anion geometries obtained using the second-order Mo/ller–Plesset perturbation theory (MP2) method. The same approach was also used to determine the...

Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase

Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexible in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of Cα and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H2-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.

Substrate channel in nitrogenase revealed by a molecular dynamics approach.

Mo-dependent nitrogenase catalyzes the biological reduction of N2 to two NH3 molecules at FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized submicrosecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel. The viability of this observed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, resulting in the discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment and that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

Retention of Conformational Entropy upon Calmodulin Binding to Target Peptides Is Driven by Transient Salt Bridges

Calmodulin (CaM) is a highly flexible calcium-binding protein that mediates signal transduction through an ability to differentially bind to highly variable binding sequences in target proteins. To identify how binding affects CaM motions, and its relationship to conformational entropy and target peptide sequence, we have employed fully atomistic, explicit solvent molecular dynamics simulations of unbound CaM and CaM bound to five different target peptides. The calculated CaM conformational binding entropies correlate with experimentally derived conformational entropies with a correlation coefficient R(2) of 0.95. Selected side-chain interactions with target peptides restrain interhelical loop motions, acting to tune the conformational entropy of the bound complex via widely distributed CaM motions. In the complex with the most conformational entropy retention (CaM in complex with the neuronal nitric oxide synthase binding sequence), Lys-148 at the C-terminus of CaM forms transient salt bridges alternating between Glu side chains in the N-domain, the central linker, and the binding target. Additional analyses of CaM structures, fluctuations, and CaM-target interactions illuminate the interplay between electrostatic, side chain, and backbone properties in the ability of CaM to recognize and discriminate against targets by tuning its conformational entropy, and suggest a need to consider conformational dynamics in optimizing binding affinities.