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Protein folding kinetics and thermodynamics from atomistic simulations
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
2006 (engelsk)Inngår i: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 96, nr 23, s. 238102-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Determining protein folding kinetics and thermodynamics from all-atom molecular dynamics (MD) simulations without using experimental data represents a formidable scientific challenge because simulations can easily get trapped in local minima on rough free energy landscapes. This necessitates the computation of multiple simulation trajectories, which can be independent from each other or coupled in some manner, as, for example, in the replica exchange MD method. Here we present results obtained with a new analysis tool that allows the deduction of faithful kinetics data from a heterogeneous ensemble of simulation trajectories. The method is demonstrated on the decapeptide Chignolin for which we predict folding and unfolding time constants of 1.0±0.3 and 2.6±0.4  μs, respectively. We also derive the energetics of folding, and calculate a realistic melting curve for Chignolin.

sted, utgiver, år, opplag, sider
2006. Vol. 96, nr 23, s. 238102-
Emneord [en]
Computer Simulation, Kinetics, Models; Chemical, Models; Molecular, Protein Folding, Proteins/*chemistry/*ultrastructure, Quantum Theory, Research Support; Non-U.S. Gov't, Thermodynamics
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-18880DOI: 10.1103/PhysRevLett.96.238102PubMedID: 16803409OAI: oai:DiVA.org:uu-18880DiVA, id: diva2:46652
Tilgjengelig fra: 2006-11-23 Laget: 2006-11-23 Sist oppdatert: 2017-12-08bibliografisk kontrollert
Inngår i avhandling
1. Protein Folding and DNA Origami
Åpne denne publikasjonen i ny fane eller vindu >>Protein Folding and DNA Origami
2010 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

In this thesis, the folding process of the de novo designed polypeptide chignolin was elucidated through atomic-scale Molecular Dynamics (MD) computer simulations. In a series of long timescale and replica exchange MD simulations, chignolin’s folding and unfolding was observed numerous times and the native state was identified from the computed Gibbs free-energy landscape. The rate of the self-assembly process was predicted from the replica exchange data through a novel algorithm and the structural fluctuations of an enzyme, lysozyme, were analyzed.

DNA’s structural flexibility was investigated through experimental structure determination methods in the liquid and gas phase. DNA nanostructures could be maintained in a flat geometry when attached to an electrostatically charged, atomically flat surface and imaged in solution with an Atomic Force Microscope. Free in solution under otherwise identical conditions, the origami exhibited substantial compaction, as revealed by small angle X-ray scattering. This condensation was even more extensive in the gas phase.

Protein folding is highly reproducible. It can rapidly lead to a stable state, which undergoes moderate fluctuations, at least for small structures. DNA maintains extensive structural flexibility, even when folded into large DNA origami.

One may reflect upon the functional roles of proteins and DNA as a consequence of their atomic-level structural flexibility. DNA, biology’s information carrier, is very flexible and malleable, adopting to ever new conformations. Proteins, nature’s machines, faithfully adopt highly reproducible shapes to perform life’s functions robotically.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2010. s. 43
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 724
Emneord
protein folding, Molecular Dynamics simulations, DNA origami
HSV kategori
Forskningsprogram
Fysik med inriktning mot biofysik
Identifikatorer
urn:nbn:se:uu:diva-121549 (URN)978-91-554-7756-1 (ISBN)
Disputas
2010-04-20, B21, Husargatan 3, 751 24 Uppsala, BMC, 10:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2010-03-29 Laget: 2010-03-25 Sist oppdatert: 2011-03-04

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