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Schulten, Klaus J. Cohen, Jordi 2012-06-07T21:35:28Z 2012-06-07T21:35:28Z 10000-01-01 2007 "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." Submitted by William Weathers (weathrs2@illinois.edu) on 2012-06-07T21:35:28Z No. of bitstreams: 1 2007_cohen.pdf: 5685196 bytes, checksum: 3aa8a8a75003c8b00d844895e5abe73f (MD5) Made available in DSpace on 2012-06-07T21:35:28Z (GMT). No. of bitstreams: 1 2007_cohen.pdf: 5685196 bytes, checksum: 3aa8a8a75003c8b00d844895e5abe73f (MD5) Previous issue date: 2007 Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by William Weathers (weathrs2@illinois.edu) on 2012-06-07T21:35:28Z Item is restricted indefinitely. Restriction data tranferred 2014-07-01T11:10:53-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: Thesis Thesis U of I Only http://hdl.handle.net/2142/31398 5635660 en ©2007 Cohen gas migrations globins oxygenases oxidases Gas migration inside proteins: Mechanism, characterization, and applications Dissertation / Thesis text Physics Physics University of Illinois at Urbana-Champaign Dissertation Ph.D.