Visualization of Protein Folding Funnels in Lattice Models

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorOliveira, Antonio B.
dc.creatorFatore, Francisco M.
dc.creatorPaulovich, Fernando V.
dc.creatorOliveira, Osvaldo N.
dc.creatorLeite, Vitor Barbanti Pereira
dc.date2014-12-03T13:08:50Z
dc.date2016-10-25T20:09:21Z
dc.date2014-12-03T13:08:50Z
dc.date2016-10-25T20:09:21Z
dc.date2014-07-10
dc.date.accessioned2017-04-06T06:14:54Z
dc.date.available2017-04-06T06:14:54Z
dc.identifierPlos One. San Francisco: Public Library Science, v. 9, n. 7, 9 p., 2014.
dc.identifier1932-6203
dc.identifierhttp://hdl.handle.net/11449/111625
dc.identifierhttp://acervodigital.unesp.br/handle/11449/111625
dc.identifier10.1371/journal.pone.0100861
dc.identifierWOS:000338763800007
dc.identifierWOS000338763800007.pdf
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0100861
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/922400
dc.descriptionProtein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e. g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3x3x3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageeng
dc.publisherPublic Library Science
dc.relationPLOS ONE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleVisualization of Protein Folding Funnels in Lattice Models
dc.typeOtro


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