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Interaction of proteins with charged macromolecules is involved in many processes in cells. First, there are many natural 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 important also for “usual” proteins, which generally are not considered as polyanions or polycations. Herein we present few examples of atomistic molecular dynamic simulations (MD) applications to elucidate the role of charge-charge interactions in the mentioned processes. First, we adopted MD simulations to elucidate the mechanism of chaperone-like action of charged polymers. Then we performed modeling of interaction of different polymers with prion protein and observed a difference in the binding and prion protein structural changes induced by the binding of two types of sulfated polyanions, whose effect on amyloid aggregation was opposite. Compared to linear polyanions, the predicted binding site of cationic pyridinium dendrimers was more “local” and covered the region which is crucial for amyloid conversion of prion protein. Electrostatic interaction of the protein can be altered due to posttranslational modifications such as glycation, sulfation or phosphorylation, which change local charge of the protein region. We have analyzed the binding of glyceraldehyde-3-phosphate dehydrogenase with nucleic acid and amyloidogenic protein alpha-synuclein. Both macromolecules have been shown to interact with anion-binding groove of glyceraldehyde-3-phosphate dehydrogenase, and the interaction is determined mainly by charge-charge interaction. We investigated an impact of protein glycation, which is associated with modification of positively charged groups of lysine (and, in less extent, arginine) to neutral or negatively charged ones. The affinity of the binding and specificity to anion-binding groove have been shown to decrease when alpha-synuclein glycation level increased. Glycation of glyceraldehyde-3-phosphate dehydrogenase influenced the binding in the same manner. These results corroborated by experimental data demonstrate the importance of posttranslational modifications associated with local charge changes. These results are of special interest since glycation of amyloidogenic proteins can be associated with progression of neurodegenerative diseases such as Parkinson’s disease or Alzheimer’s disease. The work was supported by Russian Foundation for Basic Research, project No. 16-34-60089, and Russian Federation President Fellowship for young scientists for Pavel Semenyuk, project No. 3410.2016.4.