The process of L-asparaginase encapsulation by poly (lactic-co-glycolic acid) and methoxy poly (ethylene glycol): A molecular dynamics simulation study

L-asparaginase, an enzyme that suppresses protein synthesis in tumor cells, is widely used in pediatric chemotherapy to treat children with acute lymphocytic leukemia (ALL). Currently, the therapeutic protein is licensed by US Food and Drug Administration (FDA); however, as a medication, L-asparaginase faces difficulties because of its inherent nature. As a result, various natural and synthetic polymers are employed to create protein-loaded biodegradable nano and microspheres. Herein, we investigated the impact of biocompatible synthetic polymers, including methoxy poly (ethylene glycol) (MPEG) and poly (lactic-co-glycolic acid) (PLGA) copolymers, on the structure and dynamics of L-asparaginase (EcAII) using molecular dynamics (MD) simulations. The results showed that the protein encapsulated in PLGA was more stable than in MPEG, mainly due to electrostatic interactions between the enzyme and PLGA. On the other hand, the hydrophobic and vdW interactions provided the driving force for the protein-MPEG interaction. The MD results further demonstrated that the protein's basic residues actively interact with the PLGA polymer and play critical roles in the encapsulation mechanism. Moreover, the protein's structure was preserved throughout encapsulation. We anticipate that these findings will contribute to our understanding of how L-asparaginase interacts with various polymers and copolymers.

Automated summary

In this study, the impact of biocompatible synthetic polymers on the structure and dynamics of L-asparaginase was investigated using molecular dynamics simulations. The results demonstrate that the protein encapsulated in PLGA is more stable than in MPEG, primarily due to electrostatic interactions between the enzyme and PLGA. Hydrophobic and vdW interactions are the driving force for the protein-MPEG interaction. The study also highlights the critical roles of the protein's basic residues in the encapsulation mechanism.