Optimizing Protein-Polymer Interactions in a Poly(ethylene glycol) Coarse-Grained Model

J Phys Chem B. 2018 Aug 23;122(33):7997-8005. doi: 10.1021/acs.jpcb.8b05359. Epub 2018 Aug 14.

Abstract

Increasing demand for hybrid materials that merge the synthetic and biological areas in drug industries requires in-depth knowledge of the individual components and their contributions to these complexes. Coarse-grained (CG) models developed for proteins and polymers exist, yet there is a lack of understanding of the cross interactions when these two groups of materials integrate to build a complex. In this work, we characterized the nonbonded interactions between poly(ethylene glycol) (PEG) and amino acids in a Martini CG model utilizing state-of-the-art quantum mechanics calculations of interaction energies. The parameter set proposed, was validated by assessing the polymer density in the vicinity of individual amino acids obtained from available all-atomistic molecular dynamic simulations of plasma proteins. Our results revealed the necessity of protein-polymer interaction parameterization at the CG level to avoid overestimation of polymer association when employing other PEG models within the Martini framework.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Cattle
  • Humans
  • Molecular Dynamics Simulation
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / metabolism*
  • Protein Binding
  • Serum Albumin, Bovine / chemistry
  • Serum Albumin, Bovine / metabolism*
  • Serum Albumin, Human / chemistry
  • Serum Albumin, Human / metabolism*
  • Transferrin / chemistry
  • Transferrin / metabolism*
  • Water / chemistry

Substances

  • Amino Acids
  • Transferrin
  • Water
  • Serum Albumin, Bovine
  • Polyethylene Glycols
  • Serum Albumin, Human