Molecular Dynamics Simulations for Rationalizing Polymer Bioconjugation Strategies: Challenges, Recent Developments, and Future Opportunities

The covalent modification of proteins with polymers isa well-establishedmethod for improving the pharmacokinetic properties of therapeuticallyvaluable biologics. The conjugated polymer chains of the resultinghybrid represent highly flexible macromolecular structures. As thedynamics of such systems remain rather elusive for established experimentaltechniques from the field of protein structure elucidation, moleculardynamics simulations have proven as a valuable tool for studying suchconjugates at an atomistic level, thereby complementing experimentalstudies. With a focus on new developments, this review aims to provideresearchers from the polymer bioconjugation field with a concise andup to date overview of such approaches. After introducing basic principlesof molecular dynamics simulations, as well as methods for and potentialpitfalls in modeling bioconjugates, the review illustrates how thesecomputational techniques have contributed to the understanding ofbioconjugates and bioconjugation strategies in the recent past andhow they may lead to a more rational design of novel bioconjugatesin the future.