biostudies-literatureLan PDNational Science Centre PolandNational Science Foundation Division of Molecular and Cellular BiosciencesNIGMS NIH HHS168487https://www.ebi.ac.uk/biostudies/studies/S-EPMC11260358biostudies-literatureUnknown436(6)Synonymous mutations in messenger RNAs (mRNAs) can reduce protein-protein binding substantially without changing the protein's amino acid sequence. Here, we use coarse-grain simulations of protein synthesis, post-translational dynamics, and dimerization to understand how synonymous mutations can influence the dimerization of two E. coli homodimers, oligoribonuclease and ribonuclease T. We synthesize each protein from its wildtype, fastest- and slowest-translating synonymous mRNAs in silico and calculate the ensemble-averaged interaction energy between the resulting dimers. We find synonymous mutations alter oligoribonuclease's dimer properties. Relative to wildtype, the dimer interaction energy becomes 4% and 10% stronger, respectively, when translated from its fastest- and slowest-translaJournal of molecular biologySynonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements.PMC11260358DP2 GM140926R35 GM124818Jiang YXia YLan PDSitarik ILi MSVu QVFried SDO'Brien EPTo PNissley DAfalseSynonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements.Synonymous mutations in messenger RNAs (mRNAs) can reduce protein-protein binding substantially without changing the protein's amino acid sequence. Here, we use coarse-grain simulations of protein synthesis, post-translational dynamics, and dimerization to understand how synonymous mutations can influence the dimerization of two E. coli homodimers, oligoribonuclease and ribonuclease T. We synthesize each protein from its wildtype, fastest- and slowest-translating synonymous mRNAs in silico and calculate the ensemble-averaged interaction energy between the resulting dimers. We find synonymous mutations alter oligoribonuclease's dimer properties. Relative to wildtype, the dimer interaction energy becomes 4% and 10% stronger, respectively, when translated from its fastest- and slowest-transla2024-01-01T00:00:00Z2024 Mar2026-06-01T06:42:34.199Z2025-05-18T13:26:13.297ZS-EPMC112603583834117210.1016/j.jmb.2024.168487