Presentation Title

Continued Validation Of Carbon-Deuterium Vibrational Probes As Reporters Of Protein Binding.

Start Date

November 2016

End Date

November 2016

Location

HUB 268

Type of Presentation

Oral Talk

Abstract

Vibrational spectroscopy is a powerful tool for determining structural and dynamical properties of macromolecules such as proteins. Because protein infrared spectra are generally cluttered, site-specific vibrational probes (the frequency of which is sensitive to the charge distribution in its surroundings) can be used to detect environmental changes such as protein binding. The efficacy of carbon-deuterium probes in small globular proteins to detect protein binding is investigated using combined molecular dynamics and electronic structure techniques. Using a combination of molecular dynamics and mixed quantum/classical energy calculations, the frequency of the vibrational probe was calculated. The probe was placed on three different carbon sites located on two different amino acids at various calculated distances from the active site. Human acidic fibroblast growth factor protein (PDB ID 4QO3) was chosen because it is a small globular protein that is a drug target in Homo sapiens. Two simulations with a probe on the alpha-, delta-, and epsilon-carbon of TYR12 and TYR19 were run, with and without the imidazole ligand. The magnitude in the difference in frequencies was between 19-52 cm-1 and between 10-41 cm-1 for TYR12 & TYR19 respectively. These shifts represent a significant change in a vibrational spectrum, meaning carbon-deuterium is an effective probe of binding in human acidic fibroblast growth factor.

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Nov 12th, 3:45 PM Nov 12th, 4:00 PM

Continued Validation Of Carbon-Deuterium Vibrational Probes As Reporters Of Protein Binding.

HUB 268

Vibrational spectroscopy is a powerful tool for determining structural and dynamical properties of macromolecules such as proteins. Because protein infrared spectra are generally cluttered, site-specific vibrational probes (the frequency of which is sensitive to the charge distribution in its surroundings) can be used to detect environmental changes such as protein binding. The efficacy of carbon-deuterium probes in small globular proteins to detect protein binding is investigated using combined molecular dynamics and electronic structure techniques. Using a combination of molecular dynamics and mixed quantum/classical energy calculations, the frequency of the vibrational probe was calculated. The probe was placed on three different carbon sites located on two different amino acids at various calculated distances from the active site. Human acidic fibroblast growth factor protein (PDB ID 4QO3) was chosen because it is a small globular protein that is a drug target in Homo sapiens. Two simulations with a probe on the alpha-, delta-, and epsilon-carbon of TYR12 and TYR19 were run, with and without the imidazole ligand. The magnitude in the difference in frequencies was between 19-52 cm-1 and between 10-41 cm-1 for TYR12 & TYR19 respectively. These shifts represent a significant change in a vibrational spectrum, meaning carbon-deuterium is an effective probe of binding in human acidic fibroblast growth factor.