Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications

Abstract

Interaction of proteins with charged macromolecules is involved in many processes in cells. Firstly, there are many naturally occurred charged polymers such as DNA and RNA, polyphosphates, sulfated glycosaminoglycans, etc., as well as pronouncedly charged proteins such as histones or actin. Electrostatic interactions are also important for “generic” proteins, which are not generally considered as polyanions or polycations. Finally, protein behavior can be altered due to post-translational modifications such as phosphorylation, sulfation, and glycation, which change a local charge of the protein region. Herein we review molecular modeling for the investigation of such interactions, from model polyanions and polycations to unfolded proteins. We will show that electrostatic interactions are ubiquitous, and molecular dynamics simulations provide an outstanding opportunity to look inside binding and reveal the contribution of electrostatic interactions. Since a molecular dynamics simulation is only a model, we will comprehensively consider its relationship with the experimental data.

Alpha-Synuclein Amyloid Aggregation Is Inhibited by Sulfated Aromatic Polymers and Pyridinium Polycation

“…The obtained results are of special interest as a model of interactions that occur in humans during the development and propagation of amyloidosis associated with alpha-synuclein. Human cells contain many charged polymers, including heparan sulfate and other sulfated glycosaminoglycans [37]. Their influence on amyloidogenic proteins, including alpha-synuclein, was studied in a few works [34][35][36]43].…”

“…Thus, heparin and heparan sulfate were shown to induce amyloid aggregation of apolipoprotein A-I [34,35] and serum amyloid A [36]. Noteworthy, electrostatic interactions are of special importance for amyloid aggregation [37]. The results of the inhibition of amyloid aggregation by synthetic polymers have also been described.…”

Oral delivery of proteins and peptides: Challenges, status quo and future perspectives

“…Some polymers are employed to encapsulate PPs for improving the stability or controlling the release. But the hydrophobic domain and charges of polymers can influence the stability of PPs, such as aggregation or adsorption 103 , 104 .…”

Effect of Polyphosphorylation on Behavior of Protein Disordered Regions

“…Protein interaction with charged polymers (so-called polyelectrolytes), including highly charged proteins and other biological macromolecules [1], is of special relevance for many key processes. One of "classic" polyelectrolytes is inorganic polyphosphates, which were found in many organisms.…”