The Aβ1-42 dimer is the smallest oligomer of the 42-residue Aβ peptide (Aβ1-42), which is involved in Alzheimer's disease. The molecular tweezer CLR01 is a synthetic molecule that selectively binds lysine and arginine residues to inhibit toxic aggregation of amyloidogenic peptides. Here, we performed replica exchange molecular dynamics simulations of Aβ1-42 in explicit water to study, at the molecular level, the effect of CLR01 binding to the lysine and arginine residues in the dimer. We found that CLR01 molecules encapsulate both lysine residues of each Aβ1-42 monomer while only establishing labile interactions with the arginine residues. This encapsulation leads to the noncovalent disruption of inter- and intramolecular interactions involving the monomers. Additionally, the total β-sheet content in the Aβ1-42 dimer decreases because of this binding. With CLR03, a negative control molecule that shares the charged core of CLR01 but does not form inclusion complexes, Aβ1-42 dimer formation is observed, similar to the reference system without ligands. Our work allows establishing a molecular mechanism for the modulation of protein-protein interactions in Aβ1-42 by CLR01. This mechanism is characterized by an aggregation pathway driven by the encapsulation of lysine residues as well as by the secondary interactions of tweezers with the peptide units and with other CLR01 molecules.