In clinical settings, high-dose IL-2 can be used due to its anti-cancer properties. However, there are many problems encountered in this therapy such as toxicity and other side effects. To improve IL-2 based immunotherapies, researchers have studied modified forms of IL-2, including single-point variants of IL-2. In this study, we aimed to study the effect of single-point mutations in IL-2 (F42A, Y45A, and E61A) and its interaction with IL-2Rα. Structural modeling and molecular dynamics simulation were conducted to obtain stabilized structures of both IL-2 and its single-point variants. IL-2/IL-2 variant structures were subjected to molecular docking and interaction analyses with IL-2Rα. Moreover, Gibbs free energy calculations were performed to understand the thermodynamic aspects of interaction. Optimized high-quality structural models of wild-type IL-2 and its three single-point variants (F42A, Y45A, and E61A) were obtained by molecular modeling and simulations. Overall, our results suggest that these single-point mutations in IL-2 not only preserved the conformational compactness of IL-2 but also enhanced its interaction with cognate IL-2 receptor. The obtained results are in conformity with previous studies and may be helpful to guide the designing of novel IL-2 mutants to improve cancer immunotherapy.

Keywords: Human Interleukin-2; Structural modeling; Molecular dynamics; Docking; In-silico interaction