Continuation of Vibrational Optical Activity studies of proteins, peptides and nucleic acids with an emphasis on applications of vibrational circular dichroism (VCD) to structural analysis are proposed. Systematic interpretation of VCD data coupled to data from other spectroscopic techniques employing statistically based models will be used to refine the information obtainable from spectroscopic studies of such molecules. VCD samples the chiral nature of localized transitions of a biomolecule in its ground electronic state and yields data shown to be highly sensitive to structural variation. Statistical data analysis algorithms developed for protein spectral analysis have demonstrated an ability to predict secondary structure from spectra that in some cases has an advantage over conventional electronic CD and FTlR based techniques. Coupling all of this spectral information can lead to its more reliable application. Specifically the project will entail: 1. VCD instrumental development to improve sensitivity through use of step-scan FTlR techniques. This will include extension of the data base to include protein spectra in 1-120 solution, avoiding the need for deuterium exchange. 2. Analysis of segment length, folding pattern and environmental effects on the observed spectra. 3. Neural network analysis of spectra in terms of structure using both secondary structure descriptors and environmental aspects (such as folding patterns). 4. Study of specific protein conformational problems related to the folding problem. 5. Study of the spectral character of model peptide systems to gain insight into the origin of the more complex bandshapes seen in protein spectra and application to oxytocin derivatives. 6. Theoretical simulation of peptide and protein VCD using quantum mechanical evaluation of near-neighbor interactions and dipolar modeling of long range interactions. 7. Determination of specific characteristic spectral forms for uniquely folded nucleic acid structures.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030147-12
Application #
3277761
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1982-02-01
Project End
1997-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Keiderling, Timothy A; Xu, Q (2002) Unfolded peptides and proteins studied with infrared absorption and vibrational circular dichroism spectra. Adv Protein Chem 62:111-61
Silva, R A Gangani D; Yasui, Sritana C; Kubelka, Jan et al. (2002) Discriminating 3(10)- from alpha-helices: vibrational and electronic CD and IR absorption study of related Aib-containing oligopeptides. Biopolymers 65:229-43
Baello, B I; Pancoska, P; Keiderling, T A (2000) Enhanced prediction accuracy of protein secondary structure using hydrogen exchange Fourier transform infrared spectroscopy. Anal Biochem 280:46-57
Bour, P; Kubelka, J; Keiderling, T A (2000) Simulations of oligopeptide vibrational CD: effects of isotopic labeling. Biopolymers 53:380-95
Pancoska, P; Janota, V; Keiderling, T A (1999) Novel matrix descriptor for secondary structure segments in proteins: demonstration of predictability from circular dichroism spectra. Anal Biochem 267:72-83
Silva, R A; Sherman, S A; Keiderling, T A (1999) Beta-hairpin stabilization in a 28-residue peptide derived from the beta-subunit sequence of human chorionic gonadotropin hormone. Biopolymers 50:413-23
Keiderling, T A; Silva, R A; Yoder, G et al. (1999) Vibrational circular dichroism spectroscopy of selected oligopeptide conformations. Bioorg Med Chem 7:133-41
Lusitani, D; Menhart, N; Keiderling, T A et al. (1998) Ionic strength effect on the thermal unfolding of alpha-spectrin peptides. Biochemistry 37:16546-54
Wi, S; Pancoska, P; Keiderling, T A (1998) Predictions of protein secondary structures using factor analysis on Fourier transform infrared spectra: effect of Fourier self-deconvolution of the amide I and amide II bands. Biospectroscopy 4:93-106
Yoder, G; Pancoska, P; Keiderling, T A (1997) Characterization of alanine-rich peptides, Ac-(AAKAA)n-GY-NH2 (n = 1-4), using vibrational circular dichroism and Fourier transform infrared. Conformational determination and thermal unfolding. Biochemistry 36:15123-33

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