Molecular dynamics investigation of halogenated amyloidogenic peptides
Besides their biomolecular relevance, amyloids, generated by the self-assembly of peptides and proteins, are highly organized structures useful for nanotechnology applications. The introduction of halogen atoms in these peptides, and thus the possible formation of halogen bonds, allows further possibilities to finely tune the amyloid nanostructure. In this work, we performed molecular dynamics simulations on different halogenated derivatives of the β-amyloid peptide core-sequence KLVFF, by using a modified AMBER force field in which the σ-hole located on the halogen atom is modeled with a positively charged extra particle. The analysis of equilibrated structures shows good agreement with crystallographic data and experimental results, in particular concerning the formation of halogen bonds and the stability of the supramolecular structures. The modified force field described here allows describing the atomistic details contributing to peptides aggregation, with particular focus on the role of halogen bonds. This framework can potentially help the design of novel halogenated peptides with desired aggregation propensity.
KeywordsAmyloid Peptide Self-assembly Halogen bond Molecular dynamics
The authors wish to thank Fondazione Cariplo (grant no. 2016-0481) and the H2020 EU Project AMMODIT (grant no. 645672) for funding. P.M. wishes to acknowledge the ERC for funding the project FOLDHALO (grant no. 307108) and MINIRES (grant no. 789815).
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Conflict of interest
The authors declare that they have no conflict of interest.
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