Dynamics and Thermodynamics of Transthyretin Association from Molecular Dynamics Simulations.
Molecular dynamics simulations are used in this work to probe the structural stability and the dynamics of engineered mutants of transthyretin (TTR), i.e., the double mutant F87M/L110M (MT-TTR) and the triple mutant F87M/L110M/S117E (3M-TTR), in relation to wild-type. Free energy analysis from end-p...
| Publicado en: | BioMed Research International Vol. 2018; pp. 1 - 15 |
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| Autores principales: | , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
6/5/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=129958639&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 129958639 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 6/5/2018 vid: 2018 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 129958639 129958639 129958639 10.1155/2018/7480749 129958639 ppf: 1 ppct: 14 formats: fmt: @attributes: type: P tig: atl: Dynamics and Thermodynamics of Transthyretin Association from Molecular Dynamics Simulations. aug: au: Dongmo Foumthuim, Cedrix J. Corazza, Alessandra Berni, Rodolfo Esposito, Gennaro Fogolari, Federico affil: Dipartimento di Area Medica, Università di Udine, Piazzale Kolbe 4, 33100 Udine, Italy sug: subj: Serum Albumin Analysis Mutation Kinetics Computer Simulation Molecular Structure Polymers Human ab: Molecular dynamics simulations are used in this work to probe the structural stability and the dynamics of engineered mutants of transthyretin (TTR), i.e., the double mutant F87M/L110M (MT-TTR) and the triple mutant F87M/L110M/S117E (3M-TTR), in relation to wild-type. Free energy analysis from end-point simulations and statistical effective energy functions are used to analyze trajectories, revealing that mutations do not have major impact on protein structure but rather on protein association, shifting the equilibria towards dissociated species. The result is confirmed by the analysis of 3M-TTR which shows dissociation within the first 10 ns of the simulation, indicating that contacts are lost at the dimer-dimer interface, whereas dimers (formed by monomers which pair to form two extended β-sheets) appear fairly stable. Overall the simulations provide a detailed view of the dynamics and thermodynamics of wild-type and mutant transthyretins and a rationale of the observed effects. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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