Recently we succeeded in preventing aggregation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) using polyelectrolytes. In the present work, the range of the model proteins has been extended at the expense of lysozyme and alpha-lactalbumin that are noticeably differed by isoelectric points. Experiments were performed both at higher and lower pH values than pI. In all cases, highly charged polycation or polyanion were capable of aggregation suppression. Furthermore, GAPDH was protected efficiently by both polyanion and polycation in all selected conditions. Noteworthy, in many cases protein protection was achieved by similarly charged polyelectrolyte, and the higher level of protection by polycation was achieved at lower pH despite the weakening of the Coulomb attraction. According to molecular dynamics simulations, polycation bound only negatively charged sites and formed loops and tails around protein surface. The unbound fragments seem to determine the high solubility of the complex and hence, are favorable the protein aggregation protection. The reported results could be important as a platform for the development of artificial chaperones. (C) 2016 Elsevier Ltd. All rights reserved.