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Crouzier","year":"1995","journal-title":"J Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/intimm\/5.12.1523","article-title":"Structure of the VH and VL segments of polyreactive and monoreactive human natural antibodies to HIV-1 and Escherichia coli beta-galactosidase","volume":"5","author":"N Harindranath","year":"1993","journal-title":"Int Immunol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.jmb.2008.05.042","article-title":"Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles","volume":"381","author":"S Chaudhury","year":"2008","journal-title":"J Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e1000644","DOI":"10.1371\/journal.pcbi.1000644","article-title":"SnugDock: paratope structural optimization during antibody-antigen docking compensates for errors in antibody homology models","volume":"6","author":"A 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