Determining the Potential of Mean Force for Amyloid-β Dimerization: Combining Self-Consistent Field Theory with Molecular Dynamics Simulation
| Autor: | Mark J. Uline, Symon Jahan Sajib, Melissa A. Moss, Tao Wei, Nicholas P. van der Munnik |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Amyloid beta-Peptides Dimer Temperature Charge density Hydrogen-Ion Concentration Molecular Dynamics Simulation Protein aggregation 010402 general chemistry Fibril 01 natural sciences 0104 chemical sciences Computer Science Applications 03 medical and health sciences chemistry.chemical_compound Molecular dynamics 030104 developmental biology Monomer chemistry Chemical physics Thermodynamics Field theory (psychology) Physical and Theoretical Chemistry Potential of mean force Dimerization |
| Zdroj: | Journal of Chemical Theory and Computation. 14:2696-2704 |
| ISSN: | 1549-9626 1549-9618 |
| Popis: | Amyloid-β (Aβ) protein aggregates through a complex pathway to progress from monomers to soluble oligomers and ultimately insoluble fibrils. Because of the dynamic nature of aggregation, it has proven exceedingly difficult to determine the precise interactions that lead to the formation of transient oligomers. Here, a statistical thermodynamic model has been developed to elucidate these interactions. Aβ1–42 was simulated using fully atomistic replica exchange molecular dynamics. We use an ensemble of approximately 5 × 105 configurations taken from simulation as input in a self-consistent field theory that explicitly accounts for the size, shape, and charge distribution of both the amino acids comprising Aβ and all molecular species present in solution. The solution of the model equations provides a prediction of the probabilities of the configurations of the Aβ dimer and the potential of mean force between two monomers during the dimerization process. This model constitutes a reliable methodology to eluci... |
| Databáze: | OpenAIRE |
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