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Journal article
Free energy and hidden barriers of the β-sheet structure of prion protein
Journal of chemical theory and computation, v 11(10), pp 5024-5034
13 Oct 2015
PMID: 26574287
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
On-the-fly free-energy parametrization is a new collective variable biasing approach akin to metadynamics with one important distinction: rather than acquiring an accelerated distribution via a history-dependent bias potential, sampling on this distribution is achieved from the beginning of the simulation using temperature-accelerated molecular dynamics. In the present work, we compare the performance of both approaches to compute the free-energy profile along a scalar collective variable measuring the H-bond registry of the β-sheet structure of the mouse Prion protein. Both methods agree on the location of the free-energy minimum, but free-energy profiles from well-tempered metadynamics are subject to a much higher degree of statistical noise due to hidden barriers. The sensitivity of metadynamics to hidden barriers is shown to be a consequence of the history dependence of the bias potential, and we detail the nature of these barriers for the prion β-sheet. In contrast, on-the-fly parametrization is much less sensitive to these barriers and thus displays improved convergence behavior relative to that of metadynamics. While hidden barriers are a frequent and central issue in free-energy methods, on-the-fly free-energy parametrization appears to be a robust and preferable method to confront this issue.
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Details
- Title
- Free energy and hidden barriers of the β-sheet structure of prion protein
- Creators
- S Alexis Paz - Department of Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United StatesCameron F Abrams - Department of Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United States
- Publication Details
- Journal of chemical theory and computation, v 11(10), pp 5024-5034
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000362921700049
- Scopus ID
- 2-s2.0-84944225066
- Other Identifier
- 991014877652304721
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- Web of Science research areas
- Chemistry, Physical
- Physics, Atomic, Molecular & Chemical