{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:17:47Z","timestamp":1762917467634,"version":"3.41.2"},"reference-count":61,"publisher":"AIP Publishing","issue":"21","content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,6,7]]},"abstract":"<jats:p>We performed extensive lattice Monte Carlo simulations of ribosome-bound stalled nascent chains (RNCs) to explore the relative roles of native topology and non-native interactions in co-translational folding of small proteins. We found that the formation of a substantial part of the native structure generally occurs towards the end of protein synthesis. However, multi-domain structures, which are rich in local interactions, are able to develop gradually during chain elongation, while those with proximate chain termini require full protein synthesis to fold. A detailed assessment of the conformational ensembles populated by RNCs with different lengths reveals that the directionality of protein synthesis has a fine-tuning effect on the probability to populate low-energy conformations. In particular, if the participation of non-native interactions in folding energetics is mild, the formation of native-like conformations is majorly determined by the properties of the contact map around the tethering terminus. Likewise, a pair of RNCs differing by only 1-2 residues can populate structurally well-resolved low energy conformations with significantly different probabilities. An interesting structural feature of these low-energy conformations is that, irrespective of native structure, their non-native interactions are always long-ranged and marginally stabilizing. A comparison between the conformational spectra of RNCs and chain fragments folding freely in the bulk reveals drastic changes amongst the two set-ups depending on the native structure. Furthermore, they also show that the ribosome may enhance (up to 20%) the population of low energy conformations for chains folding to native structures dominated by local interactions. In contrast, a RNC folding to a non-local topology is forced to remain largely unstructured but can attain low energy conformations in bulk.<\/jats:p>","DOI":"10.1063\/1.4808044","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T23:37:40Z","timestamp":1370475460000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Structural and energetic determinants of co-translational folding"],"prefix":"10.1063","volume":"138","author":[{"given":"Heinrich","family":"Krobath","sequence":"first","affiliation":[{"name":"Universidade de Lisboa 1 Centro de F\u00edsica da Mat\u00e9ria Condensada and Departamento de F\u00edsica, , Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal"}]},{"given":"Eugene I.","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Harvard University 2 Department of Chemistry and Chemical Biology, , 12 Oxford Street, Cambridge, Massachusetts 02138, USA"}]},{"given":"Patr\u00edcia F. N.","family":"Fa\u00edsca","sequence":"additional","affiliation":[{"name":"Universidade de Lisboa 1 Centro de F\u00edsica da Mat\u00e9ria Condensada and Departamento de F\u00edsica, , Av. Prof. Gama Pinto 2, 1649-003 Lisboa, Portugal"}]}],"member":"317","published-online":{"date-parts":[[2013,6,5]]},"reference":[{"key":"2023062522211508800_c1","doi-asserted-by":"publisher","first-page":"373102","DOI":"10.1088\/0953-8984\/21\/37\/373102","volume":"21","year":"2009","journal-title":"J. Phys.: Condens. Matter"},{"key":"2023062522211508800_c2","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1021\/cr040425u","volume":"106","year":"2006","journal-title":"Chem. 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