The proposed research will address the induction of order on solvating water by biological molecules. Our approach is a powerful combination of techniques that will allow a better analysis of this property of biological systems than is achievable with previously used technologies. Our research plan uses the temperature dependence of infrared absorption (TEIR) to directly measure the hydrogen-bonding properties of biological molecules and of the solvent surrounding them. By combining TEIR with a unique variety of solvation conditions, the water-ordering implications of single functional group differences, biomolecular size, and single or double amino acid changes will be described for the first time. The research will focus on neurological small molecule hormones related to depression since these molecules are physiologically very important, provide multiple highly similar molecules with drastically different biological activities, and allow investigation of properties that are applicable to all biological molecules. The proposed research program will provide badly needed insight into this subject.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS053399-02
Application #
7095943
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Stewart, Randall R
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$42,214
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Zelent, Bogumil; Vanderkooi, Jane M; Nucci, Nathaniel V et al. (2009) Phosphate assisted proton transfer in water and sugar glasses: a study using fluorescence of pyrene-1-carboxylate and IR spectroscopy. J Fluoresc 19:21-31
Nucci, Nathaniel V; Scott, J Nathan; Vanderkooi, Jane M (2008) Coupling of complex aromatic ring vibrations to solvent through hydrogen bonds: effect of varied on-ring and off-ring hydrogen-bonding substitutions. J Phys Chem B 112:4022-35
Scott, J Nathan; Nucci, Nathaniel V; Vanderkooi, Jane M (2008) Changes in water structure induced by the guanidinium cation and implications for protein denaturation. J Phys Chem A 112:10939-48
Nucci, Nathaniel V; Zelent, Bogumil; Vanderkooi, Jane M (2008) Pyrene-1-carboxylate in water and glycerol solutions: origin of the change of pK upon excitation. J Fluoresc 18:41-9
Dashnau, Jennifer L; Nucci, Nathaniel V; Sharp, Kim A et al. (2006) Hydrogen bonding and the cryoprotective properties of glycerol/water mixtures. J Phys Chem B 110:13670-7