1. Resolution Exchange with Tunneling for Enhanced Sampling of Protein Landscapes
- Author
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Yasar, Fatih, Ray, Alan J., and Hansmann, Ulrich H. E.
- Subjects
Physics - Computational Physics ,Physics - Biological Physics ,Quantitative Biology - Biomolecules - Abstract
Simulations of protein folding and protein association happen on timescales that are orders of magnitude larger than what can typically be covered in all-atom molecular dynamics simulations. Use of low-resolution models alleviates this problem but may reduce the accuracy of the simulations. We introduce a replica-exchange-based multiscale sampling technique that combines the faster sampling in coarse-grained simulations with the potentially higher accuracy of all-atom simulations. After testing the efficiency of our Resolution Exchange with Tunneling (ResET) in simulations of the Trp-cage protein, an often used model to evaluate sampling techniques in protein simulations, we use our approach to compare the landscape of wild type and A2T mutant Abeta 1-42 peptides. Our results suggest a mechanism by that the mutation of a small hydrophobic Alanine (A) into a bulky polar Threonine (T) may interfere with the self-assembly of Abeta - fibrils.
- Published
- 2021
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