Computational Poster Presentations

The Additivity of Noncovalent Interactions in Biological Complexes: A Computational Approach

Alexander, Vanessa

  • Vanessa M. Alexander, Stacey D. Wetmore*
  • Organization: University of Lethbridge
  • Funding: UofL

Abstract: The strength of individual interactions between DNA or RNA nucleobases and/or amino acids in proteins observed in nature cannot be easily obtained through experimental studies. However, a computational approach can be more readily used and has been used in the literature to study the interactions between two biological residues. Calculations can also be used to study the additivity of protein-DNA contacts in large biological complexes by considering the individual dimers that constitute the complex. In this poster, the strengths of contacts found in nature are predicted by overlaying the optimal calculated geometries of the monomers onto experimentally determined crystal structures. The additivity, which represents whether a complex is more or less energetically favored than the collection of the pairwise interactions between its monomers, is then calculated as the difference between the overall complex interaction energy, and the sum of all dimer energies present in the complex. The additivity of the dimer interactions in complexes composed of four to seven monomers have been calculated. Our results suggest that the additivity ranges from a stabilizing value of -5.0 kJ/mol to a destabilizing value of 9.0 kJ/mol. The complexes considered were selected based on the presence of specific amino acid-nucleobase pi-pi interactions that are of interest in the Wetmore lab, and span many different types of nucelobase-amino acid interactions.

Core Electron Bonding Energies of C3H7NO Isomers

Carter, Lee

  • Lee Carter, Mariusz Klobukowski*
  • Organization: University of Alberta
  • Funding: UofA

Abstract:

The electronic states of the valence electrons in an atom involved in chemical bonds will affect the core electron ionization potentials. These potentials may be several orders of magnitude larger than those of the valence electrons. The Schrodinger equation predicts that the valence electrons, due to radial nodes, will have density close to the nucleus. Therefore, by removing some of this density, the electrons will be subjected to increased nuclear charge. By calculating the core electron ionization potentials of different isomers, one will be able to observe how different chemical bonds of the valence electrons influence core electrons.

Molecules were constructed in Molden (z-matrix editor) using estimated parameters or experimental data if available. Using Gamess and the Moller-Plesset perturbation basis set cc-pCVTZ, the geometry of the molecules were optimized. Using the optimized geometry of the molecules, the core electrons ionization energies on each atom were calculated using the MP2 method and density functional theory (DFT) methods. This is done by assuming that the geometry of the ion (core electron removed) and neutral molecule will be identical. The difference of the two energy states equates to the core electron binding energy. Hessian calculations were also completed on each molecule. This is used to predict different stretching and bending due to absorption of infrared radiation. Predicted IR spectrum can then be constructed.

From the results it is evident that delocalizing valence bond electron orbitals will result in an increase in core electron binding energies. Comparing the results to experimental data available, it is evident that the methods used, MP2/cc-pCVTZ and DFT provide an accurate description of the molecules studied.

The Effects of Discrete Water Molecules on the Stacking and T-shaped Interactions between Adenine and Histidine

Leavens, Fern

  • Fern Leavens, Cassandra D. M. Churchill, Stacey D. Wetmore*
  • Organization: University of Lethbridge
  • Funding: UofL, NSERC

Abstract: The pi-pi interactions, including both stacking and T-shaped contacts, that take place between the DNA nucleobases and proteins are believed to play a crucial role in many biological processes. It is hoped that through better characterizing these interactions, we can understand the role of such contacts in the reactions catalyzed by specific enzymes involved in numerous biological processes, such as DNA repair. This topic is optimal for computational chemistry studies since experimental characterization of these interactions is very challenging. In the past, computational studies have assumed that all interacting molecules are in the gas phase. However, in nature, these interactions generally occur in environments where water is present. The goal of this study is to better understand the strength of nucleobase-amino acid pi-pi interactions in biologically-relevant environments. Specifically, we have used computational chemistry to study the effects of discrete water molecules on the stacking and T-shaped interactions between adenine and (neutral or protonated) histidine. Our results show that in most cases the presence of water decreases the strength of adenine-histidine stacking interactions. The effect tends to be greater on protonated dimers (protonated histidine) than neutral dimers. However, the stacking strengths of protonated systems are much greater than the corresponding neutral systems even after the weakening effect of discrete water molecules is considered. Therefore, our work shows that although solvation does affect the stacking strength in adenine-histidine systems, these effects are not large enough to change the trends calculated in the gas phase. Preliminary results suggest that similar findings will be obtained for T-shaped interactions. In addition to increasing our understanding of the chemistry of biological systems, these results have important implications regarding how to use computational chemistry to characterize stacking and T-shaped interactions involved in countless biological processes.

A Computational Study of the Additivity of T-shaped and Stacking Interactions Between the Aromatic Amino Acids and Adenine in Trimers

Millions, Elizabeth

  • Elizabeth L. Millions, Karissa Donkersgoed, Cassandra D.M. Churchill, Stacey D. Wetmore*
  • Organization: University of Lethbridge
  • Funding: UofL

Abstract: By understanding how enzymes interact with DNA during base excision repair, we may be able to design new drugs and materials that enhance the effectiveness of cancer chemotherapeutic agents and antifolate drugs. It is believed that stacking and T-shaped interactions between the aromatic amino acids and DNA nucleobases within the active sites of repair enzymes are responsible for the excision of damaged nucleobases, such as 3-methyladenine. Although difficult to determine through experimental means, the binding energies of systems involving amino acids and damaged nucleobases can be established using computational chemistry. However, before damaged nucleobases are examined, the natural bases must be considered. For this reason, this poster focuses on the interactions between neutral adenine and the aromatic amino acids in an attempt to understand the potential additive nature of individual interactions in trimer systems. Previous research in the Wetmore Lab has studied the T-shaped and stacking interaction energies of, as well as the preferred relative monomer orientations in, DNA-protein dimers, and more recently examined the simultaneous interactions of two amino acids on either side of adenine. In these studies, the binding strengths of the trimers were found to be relatively additive (i.e., equal to the sum of the two dimer interaction energies). However, the relative orientation of the amino acids did not allow for amino acid-amino acid interactions. This poster examines whether the interaction energies are additive when the amino acids are aligned such that they interact with adenine, but also have potentially large amino acid-amino acid interactions.

Computational Studies of Noncovalent Interactions Between the Natural DNA Nucleobases or the Aromatic Amino Acids and Small Molecules

Wang, Siyun

  • Siyun (Linda) Wang, Cassandra D. M. Churchill, Stacey D. Wetmore*
  • Organization: University of Lethbridge
  • Funding: NSERC, UofL

Abstract: A systematic computational study of the X-H---pi interactions between four small molecules (H2O, NH3, CH4, HF) and the natural DNA nucleobases (A,C,G,T) or the aromatic amino acids (His, Phe, Trp, and Tyr) was performed. Small computational models were used where the sugar of the nucleosides and the backbone of the amino acids were replaced with a hydrogen atom. The MP2/6-31+G(d,p) method was used since dispersion forces play a main role in these interactions. Our research shows that four different kinds of clusters exist depending on whether one, two or three X-H bonds or a heavy atom (O, N, C, and F) points toward the aromatic system. Among all combinations considered, the structure with one hydrogen atom pointing toward the pi system is usually more stable due to the potential formation of a linear hydrogen bond. With regard to the aromatic amino acids, tryptophan leads to the strongest interaction which agrees with previous literature. For the nucleic acid bases, the differences in binding energies are not very large, where guanine and cytosine have the largest binding energies, and adenine and guanine have a similar acceptor character for C-H---pi interactions. Through this work, a better understanding of T-shaped interactions involving important biomolecules has been obtained.