Resolution exchange with tunneling for enhanced sampling of protein landscapes


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Yasar F., Ray A. J., Hansmann U. H. E.

PHYSICAL REVIEW E, vol.106, no.1, 2022 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 106 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1103/physreve.106.015302
  • Journal Name: PHYSICAL REVIEW E
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Compendex, EMBASE, INSPEC, MEDLINE, zbMATH
  • Hacettepe University Affiliated: Yes

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 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.