Jan Florián

Q-Chem 2.0: A High-Performance Ab Initio Electronic Structure Program Package

Q‐Chem 2.0 is a new release of an electronic structure program package, capable of performing first principles calculations on the ground and excited states of molecules using both density functional theory and wave function‐based methods. A review of the technical features contained within Q‐Chem 2.0 is presented. This article contains brief descriptive discussions of the key physical features of all new algorithms and theoretical models, together with sample calculations that illustrate their performance.

Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor.

Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen‐binding domain (PABD) and a calmodulin (CaM)‐activated adenylyl cyclase domain. Here, we report the crystal structures of CaM‐bound EF, revealing the architecture of EF PABD. CaM has N‐ and C‐terminal domains and each domain can bind two calcium ions. Calcium binding induces the conformational change of CaM from closed to open. Structures of the EF–CaM complex show how EF locks the N‐terminal domain of CaM into a closed conformation regardless of its calcium‐loading state. This represents a mechanism of how CaM effector alters the calcium affinity of CaM and uncouples the conformational change of CaM from calcium loading. Furthermore, structures of EF–CaM complexed with nucleotides show that EF uses two‐metal–ion catalysis, a prevalent mechanism in DNA and RNA polymerases. A histidine (H351) further facilitates the catalysis of EF by activating a water to deprotonate 3′OH of ATP. Mammalian adenylyl cyclases share no structural similarity with EF and they also use two‐metal–ion catalysis, suggesting the catalytic mechanism‐driven convergent evolution of two structurally diverse adenylyl cyclases.

Mechanistic alternatives in phosphate monoester hydrolysis: What conclusions can be drawn from available experimental data?

Phosphate monoester hydrolysis reactions in enzymes and solution are often discussed in terms of whether the reaction pathway is associative or dissociative. Although experimental results for solution reactions have usually been considered as evidence for the second alternative, a closer thermodynamic analysis of observed linear free energy relationships shows that experimental information is consistent with the associative, concerted and dissociative alternatives.

Enantioselectivity of Haloalkane Dehalogenases and its Modulation by Surface Loop Engineering

Engineering of the surface loop in haloalkane dehalogenases affects their enantiodiscrimination behavior. The temperature dependence of the enantioselectivity (lnE versus 1/T) of -bromoalkanes by haloalkane dehalogenases is reversed (red data points) by deletion of the surface loop; the selectivity switches back when an additional single-point mutation is made. This behavior is not observed for -bromoesters.

Nonplanar DNA Base Pairs

Three-dimensional structures of a representative set of more than 30 hydrogen-bonded nucleic acids pairs have been studied by reliable ab initio quantum mechanical methods. We show that many hydrogen-bonded nucleic acid base pairs are intrinsically nonplanar, mainly due to the partial sp3 hybridization of nitrogen atoms of their amino groups and secondary electrostatic interactions. This finding extends the variability of intermolecular interactions of DNA bases in that i) flexibility of the base pairs is larger than has been assumed before, and ii) attractive proton-proton acceptor interactions oriented out of the base pair plane are allowed. For example, all four G-A mismatch base pairs are propeller twisted, and the energy preferences for the nonplanar structures range from less than 0.1 kcal/mol to 1.8 kcal/mol. We predict that nonplanarity of the amino group of guanine in the G(anti)...A(anti) pair of the ApG step of the d(CCAAGATTGG)2 crystal structure is an important stabilizing factor that improves the energy of this structure by almost 3 kcal/mol. Currently used empirical potentials are not accurate enough to properly cover the interactions associated with amino-group and base-pair nonplanarity.

Associative Versus Dissociative Mechanisms of Phosphate Monoester Hydrolysis: On the Interpretation of Activation Entropies

Phosphate monoester and anhydride hydrolysis is ubiquitous in biology, being involved in, amongst other things, signal transduction, energy production, and the regulation of protein function. Therefore, this reaction has understandably been the focus of intensive research. Nevertheless, the precise mechanism by which phosphate monoester hydrolysis proceeds remains controversial. Traditionally, it has been assumed and frequently implied that a near-zero activation entropy is indicative of a dissociative pathway. Herein, we examine free-energy surfaces for the hydrolysis of the methyl phosphate dianion and the methyl pyrophosphate trianion in aqueous solution. In both cases, the reaction can proceed through either compact or expansive concerted (A(N)D(N)) transition states, with fairly similar barriers. We have evaluated the activation entropies for each transition state and demonstrate that both associative and dissociative transition states have near-zero entropies of activation that are in good agreement with experimental values. Therefore, we believe that the activation entropy alone is not a useful diagnostic tool, as it depends not only on bond orders at the transition state, but also on other issues that include (but are not limited to) steric factors determining the configurational volumes available to reactants during the reaction, solvation and desolvation effects that may be associated with charge redistribution upon approaching the transition state and entropy changes associated with intramolecular degrees of freedom as the transition state is approached.

THE PREDICTION OF RAMAN SPECTRA BY DENSITY FUNCTIONAL THEORY. PRELIMINARY FINDINGS

Abstract We report the first calculations of Raman vibrational intensities by density functional theory, implemented within the Q-Chem program. Local (S-VWN) and gradient-corrected (B-LYP) DFT results are compared with experimental and Hartree-Fock results for the N 2 , HF and C 2 H 6 molecules. Preliminary indications are that local DFT compares less favorably to experiment than either Hartree-Fock or gradient-corrected DFT. The Hartree-Fock and B-LYP results are generally similar except for the HF molecule, where B-LYP is somewhat better. For all methods, best results were obtained by augmenting the basis set with diffuse polarization functions.

Scaled quantum mechanical force fields and vibrational spectra of solid state nucleic acid constituents V: thymine and uracil

Abstract The scale factors of the ab initio SCF STO-3G and MINI-1, and semiempirical PM3 harmonic force fields were determined by fitting to the Raman and IR spectra of polycrystalline uracil and thymine. Both in-plane and out-of-plane vibrational modes have been interpreted. The transferability of the scale factors between uracil and thymine and the performance of different computational methods were discussed. The Fermi resonance of the overtones of the out-of-plane deformation vibrations of oxygens with their stretching modes have been proposed as an explanation for the band splitting observed in the 1600–1800 cm−1 region of uracil.

On the intermolecular vibrational modes of the guanine⋯cytosine, adenine⋯thymine and formamide⋯formamide H-bonded dimers

Abstract Harmonic force fields, frequencies, and IR and Raman intensities of the intermolecular vibrational modes in the cyclic formamide dimer and the guanine-cytosine and adenine-thymine DNA base pairs were calculated using several ab initio methods, including Hartree-Fock, MP2 and gradient-corrected density functional theory (DFT), with various basis sets. A polar environment was modeled using the polarizable continuum model (SCRF). The effect of electron correlation upon calculated Raman intensities was investigated using DFT. The normal coordinate analysis was carried out in internal coordinates observing C2h symmetry of the formamide dimer. These coordinates were also generalized for the DNA base pairs, allowing force constants, frequencies and intensities of the characteristic intermolecular vibrational modes to be compared among the H-bonded complexes studied. In addition, coordinates defined in this way are directly related to standard DNA interbase structural parameters as pseudodyad, tilt and propeller twist angles. Extensive coupling of the intramolecular wagging vibrations of the amino groups participating in H-bonding with the tilt and propeller twist vibrations was obtained for the lowest frequency normal modes.

Computer simulation studies of the fidelity of DNA polymerases

Computer simulations can provide in principle quantitative correlation between the structures of DNA polymerases and the replication fidelity. This paper describes our progress in this direction. Using several theoretical approaches, including the free energy perturbation (FEP), linear response approximation (LRA), and the empirical valence bond (EVB) methods, we examined the stability of several mismatched base pairs in DNA duplex in aqueous solution, the contribution of binding energy to the fidelity of DNA polymerases β and T7, and the mechanism and energetics of the polymerization reaction catalyzed by T7 DNA polymerase.