Molecular Insight into the Protein–Polymer Interactions in N-Terminal PEGylated Bovine Serum Albumin

Therapeutic proteins have increasingly been used in modern medical applications, but their effectiveness is limited by factors such as stability and blood circulation time. Recently, there has been significant research into covalently linking polyethylene glycol polymer chains (PEG) to proteins, known as PEGylation, to mitigate these issues. In this work, an atomistic molecular dynamics study of N-terminal conjugated PEG-BSA (bovine serum albumin) was conducted with varying PEG molecular weights (2, 5, 10, and 20 kDa) to probe PEG-BSA interactions and evaluate the effect of polymer length on dynamics. It was found that the affinity of PEG toward the protein surface increased as a function of PEG molecular weight and that a certain weight (around 10 kDa) was required to promote protein–polymer interactions. Additionally, preferential interactions were monitored through formed contacts and hotspots were identified. PEG chains coordinating in looplike conformations were found near lysine residues. Also, it w...