Broadly neutralizing antibodies against HIV-1 are rare with the 2F5 antibody being one of the most protective. Insertion of an antibody epitope into a stable and small protein scaffold overcomes many of the obstacles found to produce antibodies. However, the design leads to grafting of epitopes that may cause protein aggregation. Here, I investigated the 2F5 epitope grafted into the Top7 as the scaffold in which the resulting immunoreactive protein precipitates along the storage time, as opposed to its completely soluble biotinylated version. Molecular dynamics showed that biotinylation eliminates the intermediate state of the scaffold-epitope Top7-2F5 by switching a noncooperative to a cooperative folding. The aggregation propensity of the Top7-designed proteins is examined in light of thermodynamic cooperativity and kinetic traps along the decreasing depth of the intermediate ensemble in the free energy landscape. This protocol may predict stable and soluble scaffold-epitopes with the purpose of composing novel therapeutic and diagnostic platforms.