Univ., Diss.--Saarbrücken, 2007.

No description available.

As the expression of the genetic blueprint, proteins are at the heart of all biological systems. The ever increasing set of available protein structures has taught us that diversity is the hallmark of their architecture, a fundamental characteristic that enables them to perform the vast array of functionality upon which all of life depends. This diversity, however, is central to one of the most challenging problems in molecular biology: how does a folding polypeptide chain navigate its way through all of the myriad of possible conformations to find its own particular biologically active form? With few overarching structural principles to draw upon that can be applied to all protein architecture, the search for a solution to the protein folding problem has yet to produce an algorithm that can explain and duplicate this fundamental biological process. In this thesis, we take a two-pronged approach for investigating the protein folding process. Our initial statistical studies of the distributions of hydrophobic and hydrophilic residues within α-helices and β-sheets suggest (i) that hydrophobicity plays a critical role in helix and sheet formation; and (ii) that the nucleation of these motifs may result in largely unidirectional growth. Most tellingly, from an examination of the amino acids found in the smallest β-sheets, we do not find any evidence of a β-nucleating code in the primary protein sequence. Complementing these statistical analyses, we have analyzed the structural environments of several ever-widening aspects of protein topology. Our examination of the gaps between strands in the smallest β-sheets reveals a common organizational principle underlying β-formation involving strands separated by large sequential gaps: with very few exceptions, these large gaps fold into single, compact structural modules, bringing the β-strands that are otherwise far apart in the sequence close together in space. We conclude, therefore, that β-nucleation in the smallest sheets results from the co-location of two strands that are either local in sequence, or local in space following prior folding events. A second study of larger β-sheets both corroborates and extends these findings: virtually all large sequential gaps between pairs of β-strands organize themselves into an hierarchical arrangement, creating a bread-crumb model of go-and-come-back structural organization that ultimately juxtaposes two strands of a parental β-structure that are far apart in the sequence in close spatial proximity. In a final study, we have formalized this go-and-come-back notion into the concept of anti-parallel double-strandedness (DS), and measure this property across protein architecture in general. With over 90% of all residues in a large, non-redundant set of protein structures classified as DS, we conclude that DS is a unifying structural principle that underpins all globular proteins. We postulate, moreover, that this one simple principle, anti-parallel double-strandedness, unites protein structure, protein folding and protein evolution. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2011-09-30 12:32:41.379

Influenza A virus is well known for its severe clinical consequences. Structurally, this virus is made up of a lipid bilayer embedded with HA, NA and M2 proteins and a core containing eight viral ribonucleoprotein (RNP) complexes. In a typical RNP complex, the nucleoprotein binds with RNA in a non specific manner. The nucleoprotein plays a vital role in transcription, replication, and packaging of RNA during infection. This study aims that NP of A/PR/8/34(H1N1) virus and A/NY/55/2004(H3N2) virus interact with different host proteins depending on cell lines and virus strains. Monoclonal antibodies targeting the nucleoprotein of these viruses have been used for immunoprecipitation and the interacting proteins were identified by mass spectrometry. Tow proteins from the cytoplasm (elongation factor 1 sigma, and Mov10 protein) and 3 proteins from the nucleus (heat shock protein70, hnRNP K protein, and anti alpha actinin 4) were found in all the viral infected cells, and were chosen for validation study. This study will help to understand the virus-host interactions in a better way and may open the gateway for the synthesis of new antiviral drugs which can block these interactions, hence controlling the infection.

Influenza A virus is well known for its severe clinical consequences. Structurally, this virus is made up of a lipid bilayer embedded with HA, NA and M2 proteins and a core containing eight viral ribonucleoprotein (RNP) complexes. In a typical RNP complex, the nucleoprotein binds with RNA in a non specific manner. The nucleoprotein plays a vital role in transcription, replication, and packaging of RNA during infection. This study aims that NP of A/PR/8/34(H1N1) virus and A/NY/55/2004(H3N2) virus interact with different host proteins depending on cell lines and virus strains. Monoclonal antibodies targeting the nucleoprotein of these viruses have been used for immunoprecipitation and the interacting proteins were identified by mass spectrometry. Tow proteins from the cytoplasm (elongation factor 1 sigma, and Mov10 protein) and 3 proteins from the nucleus (heat shock protein70, hnRNP K protein, and anti alpha actinin 4) were found in all the viral infected cells, and were chosen for validation study. This study will help to understand the virus-host interactions in a better way and may open the gateway for the synthesis of new antiviral drugs which can block these interactions, hence controlling the infection.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Abraham M. Lenhoff, Dept. of Chemical Engineering, and Eric W. Kaler, College of Engineering . Includes bibliographical references.

Thesis (M.Phil.) - University of St Andrews, March 2007.

Thesis (MS)--Montana State University--Bozeman, 2008. / Typescript. Chairperson, Graduate Committee: Mensur Dlakic. Includes bibliographical references (leaves 95-105).

Thesis (Doctoral)--Department of Theoretical Physics, Complex Systems Group, Lund University. / Includes bibliographical references.