Component of Cannabis, Cannabidiol, as a Possible Drug against the Cytotoxicity of Aβ(31–35) and Aβ(25–35) Peptides: An Investigation by Molecular Dynamics and Well-Tempered Metadynamics Simulations

[Image: see text] In this work cannabidiol (CBD) was investigated as a possible drug against the cytotoxicity of Aβ(31–35) and Aβ(25–35) peptides with the help of atomistic molecular dynamics (MD) and well-tempered metadynamics simulations. Four interrelated mechanisms of possible actions of CBD are proposed from our computations. This implies that one mechanism can be a cause or/and a consequence of another. CBD is able to decrease the aggregation of peptides at certain concentrations of compounds in water. This particular action is more prominent for Aβ(25–35), since originally Aβ(31–35) did not exhibit aggregation properties in aqueous solutions. Interactions of CBD with the peptides affect secondary structures of the latter ones. Clusters of CBD are seen as possible adsorbents of Aβ(31–35) and Aβ(25–35) since peptides are tending to aggregate around them. And last but not least, CBD exhibits binding to MET(35). All four mechanisms of actions can possibly inhibit the Aβ-cytotoxicity as discussed in this paper. Moreover, the amount of water also played a role in peptide clustering: with a growing concentration of peptides in water without a drug, the aggregation of both Aβ(31–35) and Aβ(25–35) increased. The number of hydrogen bonds between peptides and water was significantly higher for simulations with Aβ(25–35) at the higher concentration of peptides, while for Aβ(31–35) that difference was rather insignificant. The presence of CBD did not substantially affect the number of hydrogen bonds in the simulated systems.