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Computational study of water and ion distributions around biomolecules

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TitleInfo
Title
Computational study of water and ion distributions around biomolecules
Name (type = personal)
NamePart (type = family)
Nguyen
NamePart (type = given)
Hung Tien
NamePart (type = date)
1985-
DisplayForm
Hung Tien Nguyen
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Case
NamePart (type = given)
David A
DisplayForm
David A Case
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
York
NamePart (type = given)
Darrin M
DisplayForm
Darrin M York
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Olson
NamePart (type = given)
Wilma K
DisplayForm
Wilma K Olson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Pollack
NamePart (type = given)
Lois
DisplayForm
Lois Pollack
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2016
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Water and ions play a crucially important role in governing biomolecule structure, stability and function. Knowledge of how water molecules and ions distribute around proteins and nucleic acids at the molecular level has long been sought. Due to their highly mobile nature, the hydration water and ion cloud are very hard to probe with traditional experiment techniques such as X-ray crystallography, NMR or microscopy. Here we use a combination of computational approaches and X-ray scattering experiment to investigate the water and ion distribution around biomolecules. In the first part, we describe a protocol to calculate X-ray scattering profiles from atomic models of macromolecules. We show that the quality of the Reference Interaction Site Model (RISM) hydration closely approaches those from explicit molecular dynamics simulation in terms of reproducing X-ray intensity signals. The intensity profiles (which involve no adjustable parameters) match experiment and molecular dynamics simulation up to wide angle for relatively rigid biomolecules. For nucleic acid structures, we demonstrate that an improvement in the intensity calculations could be made by using the conformational ensemble obtained from MD simulation rather than using a single diffraction structure. In the second part, we extend the X-ray scattering theory and describe a novel analysis method to extract water and ion distribution from X-ray scattering experiment. The analysis complements recent experimental techniques, showing both numbers of excess solvent (water, ions) and aspects of their distributions around macromolecules. Comparisons between experimental and theoretically predicted distributions are made for molecular dynamics and RISM theory, showing that although the total X-ray patterns are very similar, the distributions from MD simulations are generally better than those from RISM. This illustrate the potential power of this analysis to guide the development of computational models of solvation. Finally, we investigate a possible use of partial molar volume and number of excess solvent (extracted from X-ray experiment and from other direct measurements) as a guide to recalibrate force fields. The partial molar volume (and the number of excess solvent) can be conceptually divided into contributions of the solute excluded volume and hydration shell. While the former depends only on the solute topology and can be computed once the solute structure is known, the latter is more “interesting” and contains valuable information about solute-solvent interaction. We show that current protein force fields reproduce reasonably the hydration shell term although more works are needed to achieve better solute-solvent interaction balance. For nucleic acids, the solute-solvent interaction is strongly overestimated and a recalibration is needed. As a proof of concept, we reoptimize the non-bonded parameters for the phosphate groups in a DNA duplex and show that the predicted partial molar volume and the number of excess hydration water around the DNA approach the experimental value. Our parameters, however, currently cannot be used for dynamics study unless a complete refit of bonded parameters is carried out. Since the nucleic acid structure depends tightly on the solute-solvent interaction, we believe that such a misbalance should be corrected in the near future.
Subject (authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
Subject (authority = ETD-LCSH)
Topic
Biomolecules
Subject (authority = ETD-LCSH)
Topic
Hydration
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6940
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvii, 124 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Hung Tien Nguyen
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T35Q4Z4S
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Nguyen
GivenName
Hung
MiddleName
Tien
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-12-21 12:20:20
AssociatedEntity
Name
HUNG NGUYEN
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 (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-01-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 30th, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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