Induced circular dichroism of thioflavin T interacting with acetylcholinesterase: A computational study

•Induced circular dichroism was modeled for thioflavin T in acetylcholinesterase.•Density functional theory was used for the modeling.•Even though ThT is flat, it exhibits large ICD due to the nearby aromatic rings.•The contributions from the nearby water molecules are much magnitude smaller.

Induced circular dichroism of thioflavin T (ThT) intercalated in acetylcholinesterase has been modeled by means of density functional theory. ThT in acetylcholinesterase is reported to be flat and thus cannot exhibit induced CD associated with a 'chiral twist' mechanism, i.e. stabilization of one of the enantiomeric forms by a chiral environment. Even so, the presence of aromatic side chains forming the cavity in which ThT is bound is predicted to induce substantial Cotton effect in ThT, of the magnitude comparable to the one predicted to originate from a 'chiral twist' mechanism. The predicted Cotton effect originates mostly from deformation of electron density of ThT by the presence of the aromatic rings, the contribution from crystallization water molecules being one order of magnitude smaller.

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