Unfolding dynamics of small peptides biased by constant mechanical forces
We show how multi-ensemble Markov state models can be combined with constant-force equilibrium simulations. Besides obtaining the unfolding/folding rates, Markov state models allow gaining detailed insights into the folding dynamics and pathways through identifying folding intermediates and misfolde...
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Published in | Molecular systems design & engineering Vol. 3; no. 1; pp. 24 - 213 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
01.02.2018
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Subjects | |
Online Access | Get full text |
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Summary: | We show how multi-ensemble Markov state models can be combined with constant-force equilibrium simulations. Besides obtaining the unfolding/folding rates, Markov state models allow gaining detailed insights into the folding dynamics and pathways through identifying folding intermediates and misfolded structures. For two specific peptides, we demonstrate that the end-to-end distance is an insufficient reaction coordinate. This problem is alleviated through constructing models with multiple collective variables, for which we employ the time-lagged independent component analysis requiring only minimal prior knowledge. Our results show that combining Markov state models with constant-force simulations is a promising strategy to bridge the gap between simulation and experiments even for medium-sized biomolecules.
We show how multi-ensemble Markov state models can be combined with constant-force equilibrium simulations. |
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ISSN: | 2058-9689 2058-9689 |
DOI: | 10.1039/c7me00080d |