{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Structural and energetic determinants of function in the heterotrimeric G-proteins","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/71171"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"The heterotrimeric G-proteins are important in \nsignal transduction that triggers important biological functions in cells of living organisms. The use of theoretical \nmodels to study these proteins gives additional insight into mechanisms of signal transduction and molecular \nrecognition events in the cell. With that objective in mind, molecular dynamics simulations of a heterotrimeric \nG-protein reveal structural and energetic differences among the states of its signaling cycle. The simulations are \nstripped explicit waters and analyzed in search of determinants of function with the help of backbone clustering and \ncontinuum electrostatic models such as Poisson-Boltzmann (PB) and generalized-Born (GB). The energies are \nbroken down into contributions from individual components corresponding to the carbonyl and amino part of the \nbackbone as well as the side chain of each residue. The results allow the identification of components that are \nimportant for folding and binding. Two interdependent results emerge from this research: continuum electrostatic \nmodels facilitate the understanding of biological systems from a theoretical point of view; and the heterotrimeric \nG-protein in its three states serves as a biologically important model for evaluating electrostatic continuum models. \nAs a preliminary work, an evaluation of the GB continuum model was done by measuring entropic differences in free \nenergy of binding from simulations in continuum and explicit solvent models; this supports the use of explicit \nsolvent for molecular dynamics and GB for measuring electrostatic binding free energies. Explicit water for \nsimulation and continuum electrostatic free energy calculations - with GB and PB - were further tested by \nsimulating a heterotrimeric G-protein in three different states for 100ns of simulation time. The degree to which GB \napproximates PB was quantified for total binding energies as well as for individual components' contributions to \nbinding energies. GB is corroborated as a reasonably good approximation to PB, but it appears to be most useful as a \nfilter of relevant components to be calculated with the more reliable PB method. The simulations of the \nheterotrimeric G-proteins were extended to 608ns, and further analysis included clustering and the calculations of \nfolding free energies in addition to binding free energies. Cluster analysis was performed on the backbone of the \nalpha-subunit revealing structural differences in sub domains and loop regions of the heterotrimeric G-protein in \nits different states. Differences in binding energies from one state of the heterotrimeric G-protein to the other \nwere used to identify and structurally characterize the interaction of important components. At the end of this work, \na detailed description of structural and energetic determinants of function in the heterotrimeric G-protein is given \nat the atomic level. This information gives important insight into the changes that the heterotrimeric G-protein \nundergo during signal transduction from theoretical models."},{"label":"dcterms.available","value":"2013-05-22T17:34:17Z"},{"label":"dcterms.contributor","value":"Green, David F, Deng, Yuefan"},{"label":"dcterms.creator","value":"Carrascal, \nNoel"},{"label":"dcterms.dateAccepted","value":"2013-05-22T17:34:17Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:46:17Z"},{"label":"dcterms.description","value":"Department of Applied Mathematics and Statistics"},{"label":"dcterms.extent","value":"159 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/1951/59597"},{"label":"dcterms.issued","value":"2011-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:46:17Z (GMT). No. of bitstreams: 3\nCarrascal_grad.sunysb_0771E_10814.pdf.jpg: 1894 bytes, checksum: a6009c46e6ec8251b348085684cba80d (MD5)\nCarrascal_grad.sunysb_0771E_10814.pdf.txt: 310471 bytes, checksum: a5a10920242e22398d0d04f80441e522 (MD5)\nCarrascal_grad.sunysb_0771E_10814.pdf: 40310841 bytes, checksum: 8152ad532b85a1f6b7ae78be083a7ca5 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Backbone Clustering, Component Analysis, Computational \nBiology, Free Energies of Binding, G-protein, Molecular Dynamics"},{"label":"dcterms.title","value":"Structural and energetic determinants of function in the heterotrimeric G-proteins"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F94%2F76%2F139476539182867654192772328566771011264/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F94%2F76%2F139476539182867654192772328566771011264","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}