Kevin Range

Accurate Proton Affinity and Gas-Phase Basicity Values for Molecules Important in Biocatalysis

Benchmark quantum calculations of proton affinities and gas-phase basicities of molecules relevant to biochemical processes, particularly acid/base catalysis, are presented and compared for a variety of multilevel and density functional quantum models. Included are nucleic acid bases in both keto and enol tautomeric forms, ribose in B-form and A-form sugar pucker conformations, amino acid side chains and backbone molecules, and various phosphates and phosphoranes, including thio substitutions. This work presents a high-level thermodynamic characterization of biologically relevant protonation states and provides a benchmark database for development of next-generation semiempirical and approximate density functional quantum models and parametrization of methods to predict pK(a) values and relative solvation energies.

Benchmark calculations of proton affinities and gas-phase basicities of molecules important in the study of biological phosphoryl transfer

Benchmark calculations of proton affinities and gas-phase basicities of molecules most relevant to biological phosphoryl transfer reactions are presented and compared with available experimental results. The accuracy of proton affinity and gas-phase basicity results obtained from several multi-level model chemistries (CBS-QB3, G3B3, and G3MP2B3) and density-functional quantum models (PBE0, B1B95, and B3LYP) are assessed and compared. From these data, a set of empirical bond enthalpy, entropy, and free energy corrections are introduced that considerably improve the accuracy and predictive capability of the methods. These corrections are applied to the prediction of proton affinity and gas-phase basicity values of important biological phosphates and phosphoranes for which experimental data does not currently exist. Comparison is made with results from semiempirical quantum models that are commonly employed in hybrid quantum mechanical/molecular mechanical simulations. Data suggest that the design of improved semiempirical quantum models with increased accuracy for relative proton affinity values is necessary to obtain quantitative accuracy for phosphoryl transfer reactions in solution, enzymes, and ribozymes.

The contribution of phosphate–phosphate repulsions to the free energy of DNA bending

DNA bending is important for the packaging of genetic material, regulation of gene expression and interaction of nucleic acids with proteins. Consequently, it is of considerable interest to quantify the energetic factors that must be overcome to induce bending of DNA, such as base stacking and phosphate–phosphate repulsions. In the present work, the electrostatic contribution of phosphate–phosphate repulsions to the free energy of bending DNA is examined for 71 bp linear and bent-form model structures. The bent DNA model was based on the crystallographic structure of a full turn of DNA in a nucleosome core particle. A Greens function approach based on a linear-scaling smooth conductor-like screening model was applied to ascertain the contribution of individual phosphate–phosphate repulsions and overall electrostatic stabilization in aqueous solution. The effect of charge neutralization by site-bound ions was considered using Monte Carlo simulation to characterize the distribution of ion occupations and contribution of phosphate repulsions to the free energy of bending as a function of counterion load. The calculations predict that the phosphate–phosphate repulsions account for ∼30% of the total free energy required to bend DNA from canonical linear B-form into the conformation found in the nucleosome core particle.

Structure and binding of Mg(II) ions and di-metal bridge complexes with biological phosphates and phosphoranes

Divalent Mg2+ ions often serve as cofactors in enzyme or ribozyme-catalyzed phosphoryl transfer reactions. In this work, the interaction of Mg2+ ions and di-metal bridge complexes with phosphates, phosphoranes, and other biological ligands relevant to RNA catalysis are characterized with density functional methods. The effect of bulk solvent is treated with two continuum solvation methods (PCM and COSMO) for comparison. The relative binding affinity for different biological ligands to Mg2+ are quantified in different protonation states. The structure and stability of the single-metal and di-metal complexes are characterized, and the changes in phosphate and phosphorane geometry induced by metal ion binding are discussed. Di-metal bridge complexes are a ubiquitous motif and the key factors governing their electrostatic stabilization are outlined. The results presented here provide quantitative characterization of metal ion binding to ligands of importance to RNA catalysis, and lay the groundwork for design of new generation quantum models that can be applied to the full biological enzymatic systems.

Laser-induced fluorescence of lightsticks

Used mini lightsticks will fluoresce when inserted in a UV laser beam, making it easy to demonstrate that light of the same color is produced in both fluorescence and chemiluminescence.