The translocation of protons across membranes plays an integral role in biological energy transduction processes such as ATP formation. Evidence suggests that the transport occurs via chains of H-bonded residues contained within transmembrane proteins. The transport is accomplished by a series of proton transfers from one residue to the next along H-bonds in the chain. Quantum chemical methods will be used in this project to investigate the proton translocation mechanism on a molecular le. As the three-dimensional structure of proteins makes for a wide diversity of different types and geometries of H-bonds that may participate in the chain, energetics of proton transfer will be calculated of various pairs of residues and for each pair, a range of systematic variations in the H-bond geometry will be considered. Comparisons of the energetics and analyses of electronic information will lead to a detailed understanding of the fundamentals of the proton transfer process. Those molecular properties that are important elements of the process such as polarizability, electronegativity, etc. will be identified. This information will enable predictions to be made about proton transfers between groups far too complex to be subjected to calculations of the required accuracy. Calculations will be performed first upon systems composed of small model of each residue to facilitate the application of very accurate theoretical techniques including large basis sets and electron correlation. The simplicity of these systems will allow a focusing of attention upon the basics of the proton transfer process without competing effects obscuring interpretation of the data. The sizes of the models will gradually be enlarged to more appropriate representations of each protein residue to ensure the reliability of the calculations. The large body of systematic data obtained from these studies will be used to determine the structural requirements of an efficient proton conduit. Possible mechanisms by which conformational changes within the protein may be coupled to modulation of the rate of proton flux will be thoroughly explored. The effects of pH upon the process will be examined by comparison of proton transfer properties of various protonation states of appropriate residues (e.g. -COOH vs. -COO-). The manner in which the local environment of the chain influences its conduction properties will be monitored by including charged and polar groups in its vicinity as well as incorporating external H-bonds into the calculations as would occur in a hydrophilic environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM029391-05
Application #
3276995
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1981-07-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Southern Illinois University Carbondale
Department
Type
Schools of Arts and Sciences
DUNS #
939007555
City
Carbondale
State
IL
Country
United States
Zip Code
62901