Gas migration inside proteins: Mechanism, characterization, and applications
Cohen, Jordi
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/2142/31398
Description
Title
Gas migration inside proteins: Mechanism, characterization, and applications
Author(s)
Cohen, Jordi
Issue Date
2007
Doctoral Committee Chair(s)
Schulten, Klaus J.
Department of Study
Physics
Discipline
Physics
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
gas migrations
globins
oxygenases
oxidases
Language
en
Abstract
"Gas migration inside proteins is a little-studied yet very important topic for many classes of proteins
such as globins, oxygenases, and oxidases, which store oxygen gas or use it for enzymatic purposes.
One reason why this process has not received prominent attention in recent years was because of
difficulties in identifying the pathways taken by oxygen or other gases diffusing inside proteins.
The reason for this difficulty is that, unlike typical ligand channels, gas pathways are not visible in
a protein's static structure. This thesis rectifies these difficulties, by addressing many of the issues
important for finding, understanding, and manipulating gas migration pathways inside proteins.
First, it is found and convincingly demonstrated, through the use of a molecular dynamics
methodology called locally-enhanced sampling and a novel volumetric oxygen accessibility map
method, applied to the hydrogenase enzyme, that gas molecules make their way not through static
channels, but through well-defined ""pathways"", which are completely defined by the details of a
protein's thermal motion. This work is then followed up with the development of a new method,
called implicit ligand sampling, which allows for the first time to completely identify and energetically
characterize every oxygen pathway inside any protein of known structure merely from the
protein's equilibrium dynamics. The protein dynamics, in this case, are collected through 10 ns-long
molecular dynamics simulations in the absence of internal gas ligands. Implicit ligand sampling is
then applied to and validated on the well-studied myoglobin oxygen-storage protein.
Finally, if one is to engineer oxygen pathways inside proteins, it is not enough to simply know
where such pathways are located, it is also important to understand how these pathways are
correlated with protein structure. For this reason, oxygen pathways were computed for a large
number of proteins from both the globin and copper-containing amine oxidase protein families.
It is found, surprisingly, that the locations of oxygen pathways are not conserevd within protein
families, and do not correlate at all with the proteins' tertiary folds. However, a statistically significant correlation was found between the proximity of certain residue types and protein oxygen
accessibility."
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.
