BIELER, Noah S., Tuomas P.J. KNOWLES, Daan FRENKEL a Robert VÁCHA. Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations. PLOS Computational Biology. San Francisco: PLOS, 2012, roč. 8, č. 10, s. "nestránkováno", 10 s. ISSN 1553-7358. doi:10.1371/journal.pcbi.1002692.
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Základní údaje
Originální název Connecting Macroscopic Observables and Microscopic Assembly Events in Amyloid Formation Using Coarse Grained Simulations
Autoři BIELER, Noah S. (756 Švýcarsko), Tuomas P.J. KNOWLES (246 Finsko), Daan FRENKEL (554 Nový Zéland) a Robert VÁCHA (203 Česká republika, garant, domácí).
Vydání PLOS Computational Biology, San Francisco, PLOS, 2012, 1553-7358.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 10403 Physical chemistry
Stát vydavatele Spojené státy
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 4.867
Kód RIV RIV/00216224:14740/12:00061327
Organizační jednotka Středoevropský technologický institut
Doi http://dx.doi.org/10.1371/journal.pcbi.1002692
UT WoS 000310568800003
Klíčová slova anglicky BETA-PEPTIDE; AGGREGATION KINETICS; MOLECULAR-DYNAMICS; PROTEIN; MECHANISM; OLIGOMERS; THERMODYNAMICS; PROPAGATION; IMPACT; OCCURS
Štítky ok, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Olga Křížová, učo 56639. Změněno: 5. 4. 2013 11:58.
Anotace
The pre-fibrillar stages of amyloid formation have been implicated in cellular toxicity, but have proved to be challenging to study directly in experiments and simulations. Rational strategies to suppress the formation of toxic amyloid oligomers require a better understanding of the mechanisms by which they are generated. We report Dynamical Monte Carlo simulations that allow us to study the early stages of amyloid formation. We use a generic, coarse-grained model of an amyloidogenic peptide that has two internal states: the first one representing the soluble random coil structure and the second one the b-sheet conformation. We find that this system exhibits a propensity towards fibrillar self-assembly following the formation of a critical nucleus. Our calculations establish connections between the early nucleation events and the kinetic information available in the later stages of the aggregation process that are commonly probed in experiments. We analyze the kinetic behaviour in our simulations within the framework of the theory of classical nucleated polymerisation, and are able to connect the structural events at the early stages in amyloid growth with the resulting macroscopic observables such as the effective nucleus size. Furthermore, the free-energy landscapes that emerge from these simulations allow us to identify pertinent properties of the monomeric state that could be targeted to suppress oligomer formation.
Návaznosti
ED1.1.00/02.0068, projekt VaVNázev: CEITEC - central european institute of technology
VytisknoutZobrazeno: 8. 8. 2022 16:43