PCP and conformational motifs: applications in predicting mechanical strength, allergenicity of proteins and vaccine design

dc.contributor.advisorIwahara, Junji
dc.contributor.committeeMemberBraun, Werner
dc.contributor.committeeMemberOberhauser, Andres F
dc.contributor.committeeMemberPettitt, B. Montgomery
dc.contributor.committeeMemberGoldblum, Randall M
dc.contributor.committeeMemberRowicka-Kudlicka, Malgorzata E
dc.creatorLu, Wenzhe
dc.date.accessioned2016-05-05T21:54:00Z
dc.date.available2016-05-05T21:54:00Z
dc.date.created2014-08
dc.date.submittedAugust 2014
dc.date.updated2016-05-05T21:54:00Z
dc.description.abstractThe functions and properties of proteins are mainly determined by their amino acid sequences and 3-dimensional structures. Motifs composed of amino acids that are either continuous in sequence or cluster in space play important roles in structures and functions of proteins. The functional annotation of these motifs provides insights into the mechanism of protein structures and functions and therefore contributes to our understanding of the protein folding process, and aids in the rational design of new therapeutic drugs and vaccines. In my research, I finished three projects where I identified specific motifs based on the conservation of Physical–Chemical Properties (PCP) of amino acids that could be related to the mechanical strength of proteins, to the potential allergenicity of proteins and to the antigenic diversity of the envelope proteins of encephalitic alphaviruses. I engineered novel Immunoglobulin (Ig) domains of the muscle protein titin by introducing motifs from mechanically strong Ig domains to weak Ig domains. The Atomic Force Microscope (AFM) results showed the enhanced mechanical strength for several of the engineered proteins. I developed a scoring method to evaluate the allergenicity of query sequences based on the characteristic motifs that are specific for allergenic sequences. The validation on peanut allergens, the family of pectate lyase showed its ability to distinguish allergenic sequences from non-allergenic ones. In addition, I identified conserved antibody binding epitopes on the envelope E2 proteins of diverse encephalitic alphaviruses and designed hybrid vaccines against multiple strains of alphaviruses. Through these projects, I demonstrated that mining PCP motifs is a practical computational approach to deepen our understanding of protein functions, to generate specific hypothesis for experimental verification and to guide the rationale design of novel vaccines.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/2152.3/717
dc.subjectprotein sequence motifs
dc.subjectmechanical stability
dc.subjectallergen
dc.subjectvaccine
dc.titlePCP and conformational motifs: applications in predicting mechanical strength, allergenicity of proteins and vaccine design
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBiochemistry and Molecular Biology
thesis.degree.disciplinecomputational biology and biostatistics
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.levelDoctoral
thesis.degree.nameBiochemistry and Molecular Biology (Doctoral)

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