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Similar to other macrolides, the activity of erythromycin is far from universal, as some peptides can bypass the macrolide-obstructed exit tunnel and become partially or fully synthesized. It is unclear why, at the molecular level, some proteins can be synthesized while others cannot. Here, we use steered molecular dynamics simulations to\u00a0examine how erythromycin inhibits synthesis of the peptide ErmCL but not the peptide H-NS. By pulling these peptides through the exit tunnel of the <jats:italic>E.coli<\/jats:italic> ribosome with and without erythromycin present, we find that erythromycin directly interacts with both nascent peptides, but the force required for ErmCL to bypass erythromycin is greater than that of H-NS. The largest forces arise three to six residues from their N-terminus as they start to bypass Erythromycin. Decomposing the interaction energies between erythromycin and the peptides at this point, we find that there are stronger electrostatic and dispersion interactions with the more C-terminal residues of ErmCL than with H-NS. These results suggest that erythromycin slows or stalls synthesis of ErmCL compared to H-NS due to stronger interactions with particular residue positions along the nascent protein.<\/jats:p>","DOI":"10.1038\/s41598-018-24344-9","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T11:16:11Z","timestamp":1524050171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Erythromycin leads to differential protein expression through differences in electrostatic and dispersion interactions with nascent proteins"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-1642","authenticated-orcid":false,"given":"Hoang Linh","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang Lan","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Suan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,24]]},"reference":[{"key":"24344_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nrmicro3155","volume":"12","author":"DN Wilson","year":"2014","unstructured":"Wilson, D. 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