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Macromolecular association equilibria
Descriptive
TitleInfo
Title
Macromolecular association equilibria
SubTitle
from chimeric HRV:HIV virus/antibody interactions to modeling of protein-ligand binding free energies
Name
(type = personal)
NamePart
(type = family)
Lapelosa
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(type = given)
Mauro
NamePart
(type = date)
1980-
DisplayForm
MAURO LAPELOSA
Role
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(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Levy
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(type = given)
Ron M
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Ron M Levy
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Advisory Committee
Role
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chair
Name
(type = personal)
NamePart
(type = family)
Arnold
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(type = given)
Eddy
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Eddy Arnold
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Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Gallicchio
NamePart
(type = given)
Emilio
DisplayForm
Emilio Gallicchio
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Bromberg
NamePart
(type = given)
Yana
DisplayForm
Yana Bromberg
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-01
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
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(type = code)
eng
Abstract
Proteins are dynamical entities and they can be studied exploring statistical ensembles of conformations rather than discrete states. The dynamics of proteins can be investigated using advanced sampling techniques such as Replica Exchange Molecular Dynamics (REMD). We have used REMD to study the population of ensembles of ELDKWA epitopes coming from the membrane proximal region (MPER) of gp41, which is a protein of the human immunodeficiency virus (HIV). The epitope has been inserted onto a surface loop of a rhinovirus (HRV), the common cold virus, and the design work was aimed at finding chimeric constructs able to present the epitope in an optimal conformation which would increase the antigenic characteristics of the chimeric HRV for 2F5, a broadly neutralizing antibody of HIV. Indeed, this was carried out in an attempt to build a chimeric construct able to trigger an immune response against HIV-1. The experimental part followed the computational design and led to good binding affinities for chimeric HRVs designed in silico. Computational and experimental results were in general agreement. This is relevant because it is a well designed use of molecular dynamics for protein design in order to develop vaccine constructs able to bind to a HIV broadly neutralizing antibody such as 2F5. From the epitope-antibody interactions we started to develop ideas about free energy in molecular associations and we moved our attention to free energy calculation methods. This led to the development of a binding energy distribution analysis method (BEDAM) to calculate the standard binding free energy. BEDAM was tested on a T4 lysozyme protein. The calculations were performed with a set of known binders and non-binders of the L99A and L99A/M102Q mutants of T4 lysozyme receptor. We also studied the dependence of binding volume on the free energy calculated by BEDAM and we showed that the free energy converged at an optimal value of the binding volume. The method was able to discriminate without error binders from non-binders, and the computed standard binding free energies of the binders are found to be in good agreement with experimental measurements. Finally, we also carried out BEDAM calculations on a pharmaceutical target, the FKBP12 protein, and we analyzed binding energies distributions and transitions from unbound to bound states.
Subject
(authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_3696
PhysicalDescription
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electronic resource
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application/pdf
InternetMediaType
text/xml
Extent
viii, 145 p. : ill.
Note
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Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Mauro Lapelosa
Subject
(authority = ETD-LCSH)
Topic
HIV (Viruses)
Subject
(authority = ETD-LCSH)
Topic
HIV antibodies
Subject
(authority = ETD-LCSH)
Topic
Antigenic determinants
Subject
(authority = ETD-LCSH)
Topic
Rhinoviruses
Identifier
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http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064141
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3TT4Q01
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
LAPELOSA
GivenName
MAURO
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2011-11-03 11:21:59
AssociatedEntity
Name
MAURO LAPELOSA
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
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2012-01-31
DateTime
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2012-08-01
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 1st, 2012.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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