{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:35:22Z","timestamp":1760888122007},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The anthrax protective antigen (PA) is a key component of the tripartite anthrax toxin. Monoclonal antibody (mAb) 14B7 and its engineered, affinity\u2010matured variants have been shown to be effective in blocking PA binding to cellular receptors and mitigating anthrax toxicity. Here, we perform computational structural modeling of the mAb 14B7\u2010PA interaction. Our objectives are to determine the structure of the 14B7\u2010PA complex, to deduce a structural explanation for the affinity maturation from the docking models, and to study the effect of inaccuracies in the antibody homology model on docking. We used the RosettaDock program to dock PA with the mAb 14B7 crystal structure or homology model. Our simulations generate two distinct binding orientations consistent with experimental residue mutations that diminish 14B7\u2010PA binding. Furthermore, the models suggest new site\u2010directed mutations to positively identify one of these two solutions as the correct 14B7\u2010PA docking orientation. The models indicate that PA regions 648\u2013660 and 712\u2013720 may be important for 14B7 binding in addition to the known PA epitope, and the binding interfaces are similar to that seen in the PA complex with cellular receptor CMG2. Antibody residues involved in affinity maturation do not contact the antigen in the docking models, suggesting that affinity maturation in the 14B7 family does not result from direct enhancements of antibody\u2013antigen contacts. Docking the homology model produces low\u2010resolution representations of the crystal structure docking orientations, but homology model docking is frustrated by antibody H3 loop conformation errors. This work demonstrates the usefulness and limitations of computational structure prediction for the development of antibody therapeutics, and reemphasizes the need for flexible backbone docking algorithms to achieve high\u2010resolution docking using homology models. Proteins 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.21595","type":"journal-article","created":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T20:50:16Z","timestamp":1186001416000},"page":"218-230","source":"Crossref","is-referenced-by-count":28,"title":["Modeling the structure of mAb 14B7 bound to the anthrax protective antigen"],"prefix":"10.1002","volume":"70","author":[{"given":"Arvind","family":"Sivasubramanian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Maynard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey 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