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We observe a range of divergent contact types including salt bridges, hydrogen bonds, hydrophilic interactions, and hydrophobic interactions, pointing to the frustration between competing interactions. Additionally, we find evidence of competing water-mediated interactions. Divergence in water-mediated interactions may be found to supplement existing direct contacts, but they are also found to be independent of such changes. Water-mediated contacts facilitate interactions between residues of like charge as observed in the simulation. Our results provide insight into the complexity of the dynamic native state of a globular protein and directly probe the residual frustration in the native state.<\/jats:p>","DOI":"10.1073\/pnas.0801850105","type":"journal-article","created":{"date-parts":[[2008,7,30]],"date-time":"2008-07-30T03:24:28Z","timestamp":1217388268000},"page":"10659-10664","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions"],"prefix":"10.1073","volume":"105","author":[{"given":"Christopher Kroboth","family":"Materese","sequence":"first","affiliation":[{"name":"*Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290; and"}]},{"given":"Christa Charisse","family":"Goldmon","sequence":"additional","affiliation":[{"name":"Jordan High School, Durham, NC 27707"}]},{"given":"Garegin A.","family":"Papoian","sequence":"additional","affiliation":[{"name":"*Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290; and"}]}],"member":"341","published-online":{"date-parts":[[2008,8,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340210302"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062559"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/j100366a002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1749933"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.881414"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physchem.48.1.545"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709915104"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060652l"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.3.404-421.2001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2003.10.008"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.35.040405.102134"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(03)00030-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp001193f"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0104(00)00115-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp020100m"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10377"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0214002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(04)74252-6"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307851100"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja034729u"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00151a027"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00051a023"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi035015z"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0494424"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-005-5366-0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(19981201)33:4<496::AID-PROT4>3.0.CO;2-1"},{"key":"e_1_3_3_27_2","first-page":"10894","article-title":"Free energy disconnectivity graphs: Application to peptide models","volume":"117","author":"Becker OM","year":"1997","unstructured":"OM Becker, M Karplus, Free energy disconnectivity graphs: Application to peptide models. 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