Computer simulation of titration behavior in proteins
Gibas, Cynthia Jeanne
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/22269
Description
Title
Computer simulation of titration behavior in proteins
Author(s)
Gibas, Cynthia Jeanne
Issue Date
1996
Doctoral Committee Chair(s)
Subramaniam, Shankar
Wraight, Colin A.
Department of Study
Biophysics and Computational Biology
Discipline
Biophysics and Computational Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Biophysics, General
Language
eng
Abstract
The pH dependent properties of proteins can be successfully modeled using continuum electrostatic methods provided that a sufficiently detailed and accurate model of the protein system is used. In this work, the effects of conformational changes on calculated pK$\rm\sb{a}$ values in peptide and protein systems are investigated, and it is found that an ensemble of structures may be the best representation of a protein to use for the calculation of pH-dependent properties. Studies of the effects of inclusion of explicit water molecules in the continuum electrostatic model show that this modification may improve results when an optimal number of water molecules is used. A modification to the continuum electrostatics-based multiple site titration theory based on solvent accessibility is proposed, and it is shown that this model results in improved agreement of calculated pK$\rm\sb{a}$ values with experiment when a low protein interior dielectric constant is used. The techniques developed are applied to two large protein systems. A trio of antibody/lysozyme complexes which differ minimally in epitope and paratope structure, but have widely varying association constants, are studied. In addition to electrostatic techniques, results of contact mapping and molecular surface area and volume calculations aid in the understanding of the differing properties of these systems. Several modeled mutant structures of each antibody and lysozyme are also examined. Each of these is predicted to associate less strongly with its counterpart than in the wild type. The photosynthetic reaction center of Rb. sphaeroides is studied, with some success in reproducing its known pH-dependent proton uptake. Mutants in which two critical residues in the secondary quinone binding site of the reaction center are altered are shown to be proton uptake impaired, with respect to the wild type.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
