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QM guided computational enzyme design
Descriptive
TitleInfo
Title
QM guided computational enzyme design
Name
(type = personal)
NamePart
(type = family)
Lu
NamePart
(type = given)
Beidi
NamePart
(type = date)
1990-
DisplayForm
Beidi Lu
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
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Baum
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Jean
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Jean Baum
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Advisory Committee
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chair
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York
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Darrin
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Darrin York
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Advisory Committee
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internal member
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Case
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David
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David Case
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Advisory Committee
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internal member
Name
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(type = family)
Khare
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Sagar
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Sagar Khare
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Advisory Committee
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internal member
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Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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school
TypeOfResource
Text
Genre
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theses
OriginInfo
DateCreated
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2014
DateOther
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(type = degree)
2014-10
CopyrightDate
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2014
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
PT3 is a redesigned adenosine deaminase that could catalyze the hydrolysis of organophosphate. In this present work, we evaluate the impact of previous designed mutations by investigating the mechanism of PT3. We started from the high-resolution crystal structure and truncated the active site residues as the QM model. Then the potential surface of the reaction was discovered by locating the transition states and intermediates along the reaction path with QM method B3LYP. The results showed a similar energy profile compared to natural phosphotriesterase and the nucleophilic attack turned out to be the rate-limiting step. The impact of a single mutation V218F that leaded to 20-fold increase in the catalytic rate kcat was rationalized by including this residue in QM model and a 5.0 kcal/mol difference of the reaction barrier was discovered. Then with the rationalized model, we performed a low-level QM calculation with key bond lengths fixed at a value from high-level QM results. The barrier difference of V218F changed to 3.6kcal/mol, which was still consistent with experimental results while the computation time was cut half. With this fast computational setting, we are able to analyze more mutations of their impact on the reaction barrier quantum mechanically.
Subject
(authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject
(authority = ETD-LCSH)
Topic
Enzymes--Design
Subject
(authority = ETD-LCSH)
Topic
Quantum theory
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
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ETD_5931
PhysicalDescription
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (iv, 20 p. : ill.)
Note
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M.S.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Beidi Lu
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3445K5W
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Lu
GivenName
Beidi
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2014-09-28 23:48:49
AssociatedEntity
Name
Beidi Lu
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime
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(qualifier = exact);
(point = start)
2014-10-31
DateTime
(encoding = w3cdtf);
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(point = end)
2016-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
OperatingSystem
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windows xp
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