Claudio A. Morgado

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.

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.

Balance of Attraction and Repulsion in Nucleic-Acid Base Stacking: CCSD(T)/Complete-Basis-Set-Limit Calculations on Uracil Dimer and a Comparison with the Force-Field Description

We have carried out reference quantum-chemical calculations for about 100 geometries of the uracil dimer in stacked conformations. The calculations have been specifically aimed at geometries with unoptimized distances between the monomers including geometries with mutually tilted monomers. Such geometries are characterized by a delicate balance between local steric clashes and local unstacking and had until now not been investigated using reference quantum-mechanics (QM) methods. Nonparallel stacking geometries often occur in nucleic acids and are of decisive importance, for example, for local conformational variations in B-DNA. Errors in the short-range repulsion region would have a major impact on potential energy scans which were often used in the past to investigate local geometry variations in DNA. An incorrect description of such geometries may also partially affect molecular dynamics (MD) simulations in applications when quantitative accuracy is required. The reference QM calculations have been carried out using the MP2 method extrapolated to the complete basis-set limit and corrected for higher-order electron-correlation contributions using CCSD(T) calculations with a medium-sized basis set. These reference calculations have been used as benchmark data to test the performance of the DFT-D, SCS(MI)-MP2, and DFT-SAPT QM methods and of the AMBER molecular-mechanics (MM) force field. The QM methods show close to quantitative agreement with the reference data, albeit the DFT-D method tends to modestly exaggerate the repulsion of steric clashes. The force field in general also provides a good description of base stacking for the systems studied here. However, for geometries with close interatomic contacts and clashes, the repulsion effects are rather severely exaggerated. The discrepancy reported here should not affect the overall stability of MD simulations and qualitative applications of the force field. However, it may affect the description of subtle quantitative effects such as the local conformational variations in B-DNA. Preliminary calculations for two H-bonded uracil base pairs, including one with a C-H···O H-bond, indicate excellent performance of the tested QM methods for all intermonomer distances. The force field, on the other hand, is less satisfactory, especially in the repulsive regions.

A QM/MM study of fluoroaromatic interactions at the binding site of carbonic anhydrase II, using a DFT method corrected for dispersive interactions

The interaction of the fluorinated benzyl ring of a series of inhibitors of carbonic anhydrase II (CAII), fluorine-substituted N-(4-sulfamylbenzoyl)benzylamines (SBB), with nearby residues in the active site has been studied using a hybrid QM/MM model. To account for the important dispersive interactions between the fluorinated benzenes and these residues, a density functional method with an empirical dispersive term, (DFT-D), is used as the QM part of the model. The major interactions are found to be between the substituted benzenes and the aromatic ring of a nearby phenylalanine residue. However, the intermolecular separations between these two groups span a greater range than that found for comparable interactions between isolated molecules, showing the importance of interactions with other residues, which have been quantified. A decomposition of the interaction energy between the fluorobenzenes and each residue has been carried out which shows the dispersive interactions to be dominant. This work has shown that a QM(DFT-D)/MM model is a computationally feasible and accurate way of studying substrate-protein interactions.

The structure and binding energies of the van der Waals complexes of Ar and N2 with phenol and its cation, studied by high level ab initio and density functional theory calculations.

We have investigated, using both ab initio and density functional theory methods, the minimum energy structures and corresponding binding energies of the van der Waals complexes between phenol and argon or the nitrogen molecule, and the corresponding complexes involving the phenol cation. Structures were obtained at the MP2 level using a large basis, and the corresponding energies were corrected for basis set superposition error (BSSE), higher order electron correlation effects, and for basis set size. The structures of the global minima were further refined for the effects of BSSE and the corresponding binding energies were evaluated. For each neutral species, we find only a single true minimum, pi bonded for argon and OH bonded for nitrogen. For both cationic species, we find that the OH-bonded complex is preferred over other minima which we have identified as having Ar or N(2) between exogeneous atoms. The ab initio calculations are generally in excellent agreement with experimental binding energies and rotational constants. We find that the B3LYP functional is particularly poor at describing these complexes, while a density functional theory (DFT) method with an empirical correction for dispersive interactions (DFT-D) is very successful, as are some of the new functionals proposed by Zhao and Truhlar [J. Phys. Chem. A 109, 5656 (2005); J. Chem. Theory Comput. 2, 1009 (2006); Phys. Chem. Chem. Phys. 7, 2701 (2005); J. Phys. Chem. A 108, 6908 (2004)]. Both the ab initio and DFT-D methods accurately predict the intermolecular vibrational modes.

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.

Comment on "Computational model for predicting experimental RNA and DNA nearest-neighbor free energy rankings".

Recently, Johnson et al.1 reported interesting quantumchemical computations on base stacking and base pairing energies in B-DNA and A-RNA. They deduced that “there most definitely is a quantitative correlation between the quantum mechanical gas-phase stacking data and nucleic acid stability”. Such conclusion is, in our opinion, too optimistic and oversimplified. We identified several issues questioning the validity of this statement.

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.