期刊
PHYSICAL REVIEW E
卷 106, 期 1, 页码 -出版社
AMER PHYSICAL SOC
DOI: 10.1103/PhysRevE.106.015302
关键词
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资金
- National Science Foundation [MCB160005, MCB20016]
- National Institutes of Health [GM120634, GM120578]
- Scientific and Technological Research Council of Turkey (TUBITAK) under the BIDEB programs
Simulations of protein folding and protein association typically take much longer timescales than can be covered in all-atom molecular dynamics simulations. To address this challenge, researchers have introduced 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. By testing the efficiency of this technique in simulations of the Trp-cage protein and comparing the landscapes of wild-type and A2T mutant A beta(1-42) peptides, the researchers found a mechanism by which a small hydrophobic alanine (A) mutation to a bulky polar threonine (T) may interfere with the self-assembly of A beta fibrils.
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 A beta(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 A beta fibrils.
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