Construction of the Free
Energy Landscape of Peptide
Aggregation from Molecular Dynamics Simulations
Laura Riccardi
Phuong
H. Nguyen
Gerhard Stock
10.1021/ct200911w.s001
https://acs.figshare.com/articles/journal_contribution/Construction_of_the_Free_Energy_Landscape_of_Peptide_Aggregation_from_Molecular_Dynamics_Simulations/2532373
To describe the structure and dynamics of oligomers during
peptide
aggregation, a method is proposed that considers both the intramolecular
and intermolecular structures of the multimolecule system and correctly
accounts for its degeneracy. The approach is based on the “by-parts”
strategy, which partitions a complex molecular system into parts,
determines the metastable conformational states of each part, and
describes the overall conformational state of the system in terms
of a product basis of the states of the parts. Starting from a molecular
dynamics simulation of <i>n</i> molecules, the method consists
of three steps: (i) characterization of the <i>intramolecular</i> structure, that is, of the conformational states of a single molecule
in the presence of the other molecules (e.g., β-strand or random
coil); (ii) characterization of the <i>intermolecular</i> structure through the identification of all occurring aggregate
states of the peptides (dimers, trimers, etc.); and (iii) construction
of the <i>overall</i> conformational states of the system
in terms of a product basis of the <i>n</i> “single-molecule”
states and the aggregate states. Considering the Alzheimer β-amyloid
peptide fragment Aβ<sub>16–22</sub> as a first application,
about 700 overall conformational states of the trimer (Aβ<sub>16–22</sub>)<sub>3</sub> were constructed from all-atom molecular
dynamics simulation in explicit water. Based on these states, a transition
network reflecting the free energy landscape of the aggregation process
can be constructed that facilitates the identification of the aggregation
pathways.
2012-04-10 00:00:00
Free Energy Landscape
dynamics simulation
product basis
Molecular Dynamics SimulationsTo