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

Abstract

The covalent modification of proteins with polymers is a well-established method for improving the pharmacokinetic properties of therapeutically valuable biologics. The conjugated polymer chains of the resulting hybrid represent highly flexible macromolecular structures. As the dynamics of such systems remain rather elusive for established experimental techniques from the field of protein structure elucidation, molecular dynamics simulations have proven as a valuable tool for studying such conjugates at an atomistic level, thereby complementing experimental studies. With a focus on new developments, this review aims to provide researchers from the polymer bioconjugation field with a concise and up to date overview of such approaches. After introducing basic principles of molecular dynamics simulations, as well as methods for and potential pitfalls in modeling bioconjugates, the review illustrates how these computational techniques have contributed to the understanding of bioconjugates and bioconjugation strategies in the recent past and how they may lead to a more rational design of novel bioconjugates in the future.

Molecular simulation for food protein–ligand interactions: A comprehensive review on principles, current applications, and emerging trends

“…In Equation ( 8), bonded energy in food protein-ligand binding systems frequently consists of torsional, bending, and stretching energy terms. Torsional, bending, and stretching energy terms refer to the energy change of dihedral angle rotation, angle bending between three bonded atoms, and stretching of bond between two atoms, respectively (Kehrein & Sotriffer, 2023). Due to the rotations of dihedrals, two atoms may frequently be quite close to one another in space.…”