Peter, Emanuel K. (2017) Adaptive enhanced sampling with a path-variable for the simulation of protein folding and aggregation. JOURNAL OF CHEMICAL PHYSICS, 147 (21): 214902. ISSN 0021-9606, 1089-7690
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In this article, we present a novel adaptive enhanced sampling molecular dynamics (MD) method for the accelerated simulation of protein folding and aggregation. We introduce a path-variable L based on the un-biased momenta p and displacements dq for the definition of the bias s applied to the system and derive 3 algorithms: general adaptive bias MD, adaptive path-sampling, and a hybrid method which combines the first 2 methodologies. Through the analysis of the correlations between the bias and the un-biased gradient in the system, we find that the hybrid methodology leads to an improved force correlation and acceleration in the sampling of the phase space. We apply our method on SPC/E water, where we find a conservation of the average water structure. We then use our method to sample dialanine and the folding of TrpCage, where we find a good agreement with simulation data reported in the literature. Finally, we apply our methodologies on the initial stages of aggregation of a hexamer of Alzheimer's amyloid fi fragment 25-35 (A beta 25-35) and find that transitions within the hexameric aggregate are dominated by entropic barriers, while we speculate that especially the conformation entropy plays a major role in the formation of the fibril as a rate limiting factor. Published by AIP Publishing.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACCELERATED MOLECULAR-DYNAMICS; FREE-ENERGY CALCULATIONS; MONTE-CARLO METHOD; TRP-CAGE; INFREQUENT EVENTS; ALANINE DIPEPTIDE; EXPLICIT SOLVENT; LAMBDA-DYNAMICS; LOCAL ELEVATION; ALGORITHM; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:18 |
| Last Modified: | 27 Feb 2019 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1696 |
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