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dc.contributor.authorKayser, Veysel
dc.contributor.authorVoynov, Vladimir
dc.contributor.authorChennamsetty, Naresh
dc.contributor.authorTrout, Bernhardt L.
dc.contributor.authorHelk, Bernhard
dc.date.accessioned2010-03-12T19:57:57Z
dc.date.available2010-03-12T19:57:57Z
dc.date.issued2009-05
dc.date.submitted2009-04
dc.identifier.issn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1721.1/52552
dc.description.abstractTherapeutic proteins such as antibodies constitute the most rapidly growing class of pharmaceuticals for use in diverse clinical settings including cancer, chronic inflammatory diseases, kidney transplantation, cardiovascular medicine, and infectious diseases. Unfortunately, they tend to aggregate when stored under the concentrated conditions required in their usage. Aggregation leads to a decrease in antibody activity and could elicit an immunological response. Using full antibody atomistic molecular dynamics simulations, we identify the antibody regions prone to aggregation by using a technology that we developed called spatial aggregation propensity (SAP). SAP identifies the location and size of these aggregation prone regions, and allows us to perform target mutations of those regions to engineer antibodies for stability. We apply this method to therapeutic antibodies and demonstrate the significantly enhanced stability of our mutants compared with the wild type. The technology described here could be used to incorporate developability in a rational way during the screening of antibodies in the discovery phase for several diseases.en
dc.description.sponsorshipNational Center for Supercomputing Applicationsen
dc.description.sponsorshipNovartis Pharma AGen
dc.description.sponsorshipNational Science Foundation (Grant MCB060103)en
dc.language.isoen_US
dc.publisherUnited States National Academy of Sciencesen
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0904191106en
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en
dc.sourcePNASen
dc.titleDesign of therapeutic proteins with enhanced stabilityen
dc.typeArticleen
dc.identifier.citationChennamsetty, Naresh et al. “Design of therapeutic proteins with enhanced stability.” Proceedings of the National Academy of Sciences 106.29 (2009): 11937-11942. © 2010 National Academy of Sciencesen
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.approverTrout, Bernhardt L.
dc.contributor.mitauthorKayser, Veysel
dc.contributor.mitauthorVoynov, Vladimir
dc.contributor.mitauthorChennamsetty, Naresh
dc.contributor.mitauthorTrout, Bernhardt L.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen
dc.eprint.versionFinal published versionen
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
dspace.orderedauthorsChennamsetty, N.; Voynov, V.; Kayser, V.; Helk, B.; Trout, B. L.en
dc.identifier.orcidhttps://orcid.org/0000-0003-1417-9470
mit.licensePUBLISHER_POLICYen
mit.metadata.statusComplete


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