Abstract
Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule.
Highlights
Rheumatoid arthritis (RA) is a heterogeneous disease characterized by a variable disease course in different people [1,2]
Three lines are highlighted for each protein, in which the calculated characteristics are given for the intact motif (PDB), for this motif during the molecular dynamics (MD) experiment (PDB-MD), and the modified motif over the MD experiment (PDB-PTMMD), and designates values of solvent-accessible areas of intact arginine before and after modification during the experiment (SASA of Arg (Lys)/Cit, nm2; Table 2)
We observed a similar result for the solvent-accessible surface area (SASA) of the post-translational modification (PTM) site parameter, which characterizes the solvent-accessible area of the modified amino acid residue and its neighbors at a distance of three amino acid residues toward the N- and C-ends
Summary
Rheumatoid arthritis (RA) is a heterogeneous disease characterized by a variable disease course in different people [1,2]. The pathological manifestation is joint damage, which develops in a quarter of RA patients during the first three months of the disease, and approximately 75% of patients develop erosions within the first two years after diagnosis [3]. The disease is difficult to diagnose at the early stage, and it is difficult to predict the rate of joint damage progression. There are serious side effects associated with drug therapy. In this regard, early RA diagnosis is of paramount clinical importance, since the timely therapeutic intervention in RA improves the overall disease prognosis. It seems promising to create new approaches for the early diagnosis of RA and initiation of therapy in patients for whom an unfavorable outcome is likely [2]
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