Jonathan P. McNamara

Density functional and semiempirical molecular orbital methods including dispersion corrections for the accurate description of noncovalent interactions involving sulfur-containing molecules

We describe the use of density functional theory (DFT-D) and semiempirical (AM1-D and PM3-D) methods having an added empirical dispersion correction, to treat noncovalent interactions between molecules involving sulfur atoms. The DFT-D method, with the BLYP and B3LYP functionals, was judged against a small-molecule database involving sulfur-π, S-H···S, and C-H···S interactions for which high-level MP2 or CCSD(T) estimates of the structures and binding or interaction energies are available. This database was also used to develop appropriate AM1-D and PM3-D parameters for sulfur. The DFT-D, AM1-D, and PM3-D methods were further assessed by calculating the structures and binding energies for a set of eight sulfur-containing base pairs, for which high-level ab initio data are available. The mean absolute deviations (MAD) for both sets of structures shown by the DFT-D methods are 0.04 Å for the intermolecular distances and less than 0.7 kcal mol(-)(1) for the binding and interaction energies. The corresponding values are 0.3 Å and 1.5 kcal mol(-)(1) for the semiempirical methods. For the complexes studied, the dispersion contributions to the overall binding and interaction energies are shown to be important, particularly for the complexes involving sulfur-π interactions.

Enzyme-Activated Surfactants for Dispersion of Carbon Nanotubes†

N-Fluorenyl-9-methoxycarbonyl-protected amino acids are used as surfactants for carbon nanotubes and their interactions are modeled using quantum mechanical computations. These surfactants are then converted into enzymatically activated CNT surfactants that create homogeneous aqueous nanotube dispersions on-demand under constant and physiological conditions

The interaction of carbohydrates and amino acids with aromatic systems studied by density functional and semi-empirical molecular orbital calculations with dispersion corrections.

Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an added dispersion correction have been used to study stabilising carbohydrate-aromatic and amino acid-aromatic interactions. The interaction energy for three simple sugars in different conformations with benzene, all give interaction energies close to 5 kcal mol(-1). Our original parameterization of PM3 (PM3-D) seriously overestimates this value, and has prompted a reparametrization which includes a modified core-core interaction term. With two additional parameters, the carbohydrate complexes, as well as the S22 data set, are well reproduced. The new PM3 scheme (PM3-D*) is found to describe the peptide bond-aromatic ring interactions accurately and, together with the DFT-D method, it is used to investigate the interaction of six amino acids with pyrene. Whilst the peptide backbone can adopt both stacked and T-shaped structures in the complexes with similar interaction energies, there is a preference for the unsaturated ring to adopt a stacked structure. Thus, peptides in which the latter interactions are maximised are likely to be the most effective for the functionalisation of carbon nanotubes.

Calculations of hydrogen tunnelling and enzyme catalysis: a comparison of liver alcohol dehydrogenase, methylamine dehydrogenase and soybean lipoxygenase

Although the potential energy barrier for hydrogen transfer is similar for the enzymes liver alcohol dehydrogenase, methylamine dehydrogenase and soybean lipoxygenase, the degree of tunnelling is predicted to differ greatly, and is reflected by their primary kinetic isotope effects.

Assessment of QM/MM Scoring Functions for Molecular Docking to HIV-1 Protease

We explore the ability of four quantum mechanical (QM)/molecular mechanical (MM) models to accurately identify the native pose of six HIV-1 protease inhibitors and compare them with the AMBER force field and ChemScore and GoldScore scoring functions. Three QM/MM scoring functions treated the ligand at the HF/6-31G*, AM1d, and PM3 levels; the fourth QM/MM function modeled the ligand and active site at the PM3-D level. For the discrimination of native from non-native poses, solvent-corrected HF/6-31G*:AMBER and AMBER functions exhibited the best overall performance. While the electrostatic component of the MM and QM/MM functions appears important for discriminating the native pose of the ligand, the polarization contribution in the QM/MM functions was relatively insensitive to a ligands binding mode and, for one ligand, actually hindered discrimination. The inclusion of a desolvation penalty, here using a generalized Born solvent model, improved discrimination for the MM and QM/MM methods. There appeared to be no advantage to binding mode prediction by incorporating active site polarization at the PM3-D level. Finally, we found that choice of the protonation state of the aspartyl dyad in the HIV-1 protease active site influenced the ability of scoring methods to determine the native binding pose.

THE FACILE DECOMPOSITION OF CHLORINE NITRATE IN SMALL WATER CLUSTERS

Abstract High-level electronic structure calculations show that chlorine nitrate is readily hydrolysed in a cluster of six water molecules to yield HOCl/NO 3 − /H 3 O + , and readily reacts with HCl in a cluster of two water molecules to yield Cl 2 /HNO 3 .

Can the semiempirical PM3 scheme describe iron‐containing bioinorganic molecules?

A set of iron parameters for use in the semiempirical PM3 method have been developed to allow the structure and redox properties of the active sites of iron‐containing proteins to be accurately modeled, focussing on iron–sulfur, iron–heme, and iron‐only hydrogenases. Data computed at the B3LYP/6‐31G* level for a training set of 60 representative complexes have been employed. A gradient‐based optimization algorithm has been used, and important modifications of the core repulsion function have been highlighted. The derived parameters lead in general to good predictions of the structure and energetics of molecules both within and outside the training set, and overcome the extensive deficiencies of a B3LYP/STO‐3G model. Particularly encouraging is the success of the parameters in describing [4Fe‐4S] cubanes. The derived parameter set provides a starting point should greater accuracy for a more restricted range of compounds be required.

The structure and spin-states of some Fe(III) mimics of nitrile hydratase, studied by DFT and ONIOM(DFT:PM3) calculations

Density functional methods have been successful in studying the electronic structure of molecular systems containing transition metal atoms, such as metalloenzymes. However, the treatment of large systems is still very computationally demanding, and is definitely not practical for many systems of interest, due to their size. In this paper we assess the use of these methods both alone, and when combined with the semi-empirical PM3 method within an ONIOM scheme, for determining the structure and spin-dependent energetics of a series of Fe(III) model complexes that have been synthesized to mimic the active site of nitrile hydratase, a metalloenzyme that catalyses the conversion of a wide variety of nitriles to their corresponding amides. We have found that geometry optimizations employing B3LYP generally give a good description of the structure and spin-states of these complexes and that when combined with PM3 in the framework of ONIOM, the multilevel method also performs well for some of them, suggesting that the ONIOM(B3LYP:PM3) approach offers the possibility for improvement in future calibration studies. We also find that DFT and ONIOM(DFT:PM3) calculations at the experimental geometries using the BP86, PW91PW91 and B3LYP functionals can also describe the spin-state energetics of these model complexes, with DFT performing the best.

Semiempirical molecular orbital scheme to study Lanthanide(III) complexes: PM3 parameters for Europium, Gadolinium and Ytterbium

Semiempirical parameters for europium, gadolinium, and ytterbium have been developed for use in the PM3 method to allow the structure and energetics of complexes containing lanthanide(III) ions to be accurately modeled. At the semiempirical level, the lanthanide(III) ion is represented by a +3 core and has a minimal basis of 6s5d6p (9 atomic orbitals), the 4f electrons being included within the electronic core. Training sets containing up to 19 lanthanide complexes, with data computed at the density functional theory (DFT) level, have been employed for each lanthanide(III) ion. A gradient-based optimization algorithm has been used, and important modifications of the core repulsion function have been highlighted. The derived parameters lead in general to good predictions of the structure of the complexes and demonstrate improvements in the prediction of water binding energies compared to the AM1/sparkle model. For the 28 Eu(III), 28 Gd(III), and 29 Yb(III) complexes optimized at the DFT level, the PM3 average unsigned mean errors for all interatomic distances between the lanthanide(III) ion and the ligand atoms of the first coordination sphere are 0.04, 0.03, and 0.03 Å, respectively. The derived parameters are shown to be comparable to small-basis set DFT calculations in predicting the experimental structures of various lanthanide(III) complexes. The derived parameter sets provide a starting point should greater accuracy for a more restricted range of compounds be required.

Exploration of the atmospheric reactivity of N2O5 and HCl in small water clusters using electronic structure methods

High level electronic structure calculations have been used to study the gas phase reactivity of N2O5 and HCl in small neutral water clusters containing one and two water molecules. The free energy barrier decreases from 61 (uncatalysed) to 39 kJ mol−1 when catalysed by two water molecules where the reaction products involve ClNO2 and HONO2. A new pathway for the hydrolysis of N2O5 by a single water is identified with a barrier comparable to that for the uncatalysed reaction of N2O5 with HCl. The calculations predict these reactions may be important in contributing to the ozone destruction cycle. However, the calculations also suggest that heterogeneous catalysis will be favoured over the homogeneous process.