Tim M. Watson

Theoretical studies of the amide I vibrational frequencies of [Leu]-enkephalin

DFT vibrational frequency calculations on conformers of trans-N-methylacetamide + D2O clusters, and various dipeptides were used to parameterize a seven-site model for predicting the diagonal force constants of the amide I mode of arbitrary polypeptides at the EDF1/6-31+G* level. The ultimate aim of the work is to improve the accuracy of the simple ‘floating-oscillator’ method for calculating the amide I band profiles of proteins. The model describes hydrogen-bonded and distant interactions correctly, but short-range bonded effects are not well reproduced. We therefore suggest the use of a combination of lookup tables for local interactions and the seven-site model for the remainder. To test the model, we determined the vibrational frequencies of the low energy conformers of the pentapeptide, [Leu]-enkephalin at the EDF1/6-31+G* level. The model reproduced the DFT diagonal force constants well.

Molecule frame photoelectron angular distributions from oriented methyl chloride and methyl fluoride molecules

Molecule-frame photoelectron angular distributions are reported for the A band photoionization of CH3Cl and CH3F molecules whose spatial orientation is effectively fixed using an electron–ion recoil vector correlation technique. Measurements are made at various photon wavelengths with the polarization set both perpendicular and parallel to the molecular axis. Subsidiary measurements on the lab-frame distributions of photoelectrons and photofragment ions are also presented. An extensive comparison is made with the results of a multiple scattering calculation of the photoionization dynamics and a convincing description of the data is obtained. Scattering influences arising in the photon–electron and electron–ion core interactions can be distinguished as the polarization geometry and identity of the halogen atoms is varied.

Calculating vibrational frequencies of amides: From formamide to concanavalin A

The infrared (IR) is an information rich region of molecular spectra. From characteristic absorptions it is possible to determine much structural information about molecules. This has been used to a large degree in the study of protein structure as a complementary technique to circular dichroism, X-ray crystallography and NMR. However, the current understanding of protein IR spectra is predicated largely on empirical structure–spectra relationships that are not infallible. Providing a theoretical basis for protein spectra will help to reduce these problems. In this paper, we review our recent work on accurate and computationally efficient small molecule gas phase calculations and examine how point charge environments can mimic features of proteins. We then develop a general automated strategy for applying the transition dipole coupling method for computing the IR spectra of proteins. Finally, we study the effect of conformational dynamics on the amide I band of concanavalin A.

Erratum: “Modeling the amide I bands of small peptides” [J. Chem. Phys. 125, 044312 (2006)]

Thomas la Cour Jansen, Arend G. Dijkstra, Tim M. Watson, Jonathan D. Hirst, and Jasper Knoester Citation: The Journal of Chemical Physics 136, 209901 (2012); doi: 10.1063/1.4722584 View online: http://dx.doi.org/10.1063/1.4722584 View Table of Contents: http://scitation.aip.org/content/aip/journal/jcp/136/20?ver=pdfcov Published by the AIP Publishing Articles you may be interested in Single-conformation infrared spectra of model peptides in the amide I and amide II regions: Experiment-baseddetermination of local mode frequencies and inter-mode coupling J. Chem. Phys. 137, 094301 (2012); 10.1063/1.4747507 Modeling the amide I bands of small peptides J. Chem. Phys. 125, 044312 (2006); 10.1063/1.2218516 Empirical modeling of the peptide amide I band IR intensity in water solution J. Chem. Phys. 119, 11253 (2003); 10.1063/1.1622384 Dual frequency 2D-IR of peptide amide-A and amide-I modes J. Chem. Phys. 118, 7733 (2003); 10.1063/1.1570398 Self-trapping of the amide I band in a peptide model crystal J. Chem. Phys. 117, 2415 (2002); 10.1063/1.1487376

Molecular Dynamics Simulations of a Helicase

Helicases are ubiquitous enzymes involved in nucleic acid metabolism. The PcrA DNA helicase is an essential bacterial protein involved in rolling circle plasmid replication and DNA repair. Recent crystal structures of PcrA bound to DNA indicate that a flexible loop mediates a functionally important rigid‐body‐domain rotation. In this study, we report stochastic boundary molecular dynamics simulations focused on this region for wild‐type and mutants designed to increase the rigidity of the region. Residues in the region that were helix‐disfavoring, such as glycine, threonine, and others, were mutated to alanine. The simulated dynamics, analyzed with a variety of measures of structure and mobility, indicate that a few point mutations will substantially increase helix formation in this region. Subnanosecond stochastic boundary molecular dynamics simulations at several temperatures offer a rapid protocol for assessing large numbers of mutants and provides a novel strategy for the design of experiments to test the role of this flexible loop region in the function of PcrA. Proteins 2003;52:254–262.

Vibrational analysis of capped [Leu]enkephalin

The enkephalins are peptides with important biological activity. They are much more conformationally flexible than morphine, yet they bind to similar receptors with greater binding affinity. Their structures are therefore of particular interest. In this work we study the gas-phase low energy conformers of capped [Leu]enkephalin using the EDF1 density functional with the 6-31+G* basis set. The lowest energy structure found is a single β-bend structure. Calculated vibrational spectra indicate considerable scope for determination of low energy conformers from experiment.