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.
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[1]
Allen M. P., 2017, Computer simulation of liquids
[2]
[Anonymous], 2010, Quantum mechanics and path integrals, DOI 10.1063/1.3048320
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N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USAN Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA
Babin, Volodymyr
Roland, Christopher
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机构:N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA
Roland, Christopher
Sagui, Celeste
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机构:N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA
机构:
N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USAN Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA
Babin, Volodymyr
Roland, Christopher
论文数: 0引用数: 0
h-index: 0
机构:N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA
Roland, Christopher
Sagui, Celeste
论文数: 0引用数: 0
h-index: 0
机构:N Carolina State Univ, Ctr High Performance Simulat CHiPS, Raleigh, NC 27695 USA