On the Applicability of Force Fields To Study the Aggregation of Amyloidogenic Peptides Using Molecular Dynamics Simulations

Martín Carballo-Pacheco; Ahmed E Ismail; Birgit Strodel

doi:10.1021/acs.jctc.8b00579

On the Applicability of Force Fields To Study the Aggregation of Amyloidogenic Peptides Using Molecular Dynamics Simulations

J Chem Theory Comput. 2018 Nov 13;14(11):6063-6075. doi: 10.1021/acs.jctc.8b00579. Epub 2018 Oct 31.

Authors

Martín Carballo-Pacheco^{1

2}, Ahmed E Ismail^{2

3}, Birgit Strodel^{1

4}

Affiliations

¹ Institute of Complex Systems: Structural Biochemistry (ICS-6) , Forschungszentrum Jülich GmbH , 52425 Jülich , Germany.
² AICES Graduate School , RWTH Aachen University , Schinkelstraße 2 , 52062 Aachen , Germany.
³ Aachener Verfahrenstechnik, Faculty of Mechanical Engineering , RWTH Aachen University , Schinkelstraße 2 , 52062 Aachen , Germany.
⁴ Institute of Theoretical and Computational Chemistry , Heinrich Heine University Düsseldorf , Universitätstrasse 1 , 40225 Düsseldorf , Germany.

PMID: 30336669
DOI: 10.1021/acs.jctc.8b00579

Abstract

Molecular dynamics simulations play an essential role in understanding biomolecular processes such as protein aggregation at temporal and spatial resolutions which are not attainable by experimental methods. For a correct modeling of protein aggregation, force fields must accurately represent molecular interactions. Here, we study the effect of five different force fields on the oligomer formation of Alzheimer's Aβ_16-22 peptide and two of its mutants: Aβ_16-22(F19V,F20V), which does not form fibrils, and Aβ_16-22(F19L) which forms fibrils faster than the wild type. We observe that while oligomer formation kinetics depends strongly on the force field, structural properties, such as the most relevant protein-protein contacts, are similar between them. The oligomer formation kinetics obtained with different force fields differ more from each other than the kinetics between aggregating and nonaggregating peptides simulated with a single force field. We discuss the difficulties in comparing atomistic simulations of amyloid oligomer formation with experimental observables.