Understanding the role of base stacking in nucleic acids. MD and QM analysis of tandem GA base pairs in RNA duplexes.

Preceding NMR experiments show that the conformation of tandem GA base pairs, an important recurrent non-canonical building block in RNA duplexes, is context dependent. The GA base pairs adopt "sheared" N3(G)-N6(A), N2(G)-N7(A) geometry in the r(CGAG)(2) and r(iGGAiC)(2) contexts while switching to "imino" N1(G)-N1(A), O6(G)-N6(A) geometry in the r(GGAC)(2) and r(iCGAiG)(2) contexts (iC and iG stand for isocytosine and isoguanine, respectively). As base stacking is likely to be one of the key sources of the context dependence of the conformation of GA base pairs, we calculated base stacking energies in duplexes containing such base pairs, to see if this dependence can be predicted by stacking energy calculations.

Reference MP2/CBS and CCSD(T) quantum-chemical calculations on stacked adenine dimers. Comparison with DFT-D, MP2.5, SCS(MI)-MP2, M06-2X, CBS(SCS-D) and force field descriptions.

We have performed reference quantum-chemical calculations for about 130 structures of adenine dimers in stacked conformations, with special attention given to dimers that are either vertically compressed (parallel structures) or contain close interatomic contacts (non-parallel structures). Such geometries are sampled during thermal fluctuations of nucleic acids and contribute to the local conformational variability of these systems. Their theoretical characterization requires a good description of interaction energies in the short-range repulsion region.

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.

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.

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.

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.

The non-covalent functionalisation of carbon nanotubes studied by density functional and semi-empirical molecular orbital methods including dispersion corrections.

Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an added empirical dispersion correction have been used to study the binding of a series of small molecules and planar aromatic molecules to single-walled carbon nanotubes (CNTs). For the small molecule set, the PM3-D method gives a mean unsigned error (MUE) in the binding energies of 1.2 kcal mol(-1) when judged against experimental reference data for graphitic carbon.

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 use of methods involving semi-empirical molecular orbital theory to study the structure and reactivity of transition metal complexes.

The electronic structure of molecular systems containing transition metal atoms is traditionally studied using methods based on density functional theory (DFT). Although such an approach has been quite successful, the treatment of large systems, be they transition metal complexes, bioinorganic molecules or the solid state, is still extremely computationally demanding at this level, and may not be practical for many systems of interest. In this paper we describe how semi-empirical MO methods can be used to overcome these computational bottlenecks, yet still provide predictions of the necessary accuracy.