Antibody structure, prediction and redesign - PubMed (original) (raw)
Antibody structure, prediction and redesign
V Morea et al. Biophys Chem. 1997 Oct.
Abstract
So far the difficulty to predict the structure of the third hypervariable loop of the heavy chain of antibodies has represented the main limitation in modelling the complete antigen binding site. We carefully analysed all available structures of immunoglobulins searching for rules relating the loop conformation to its amino acid sequence. Here, we analyse the conformation of this loop and show that we are able to predict the conformation of the ten residues proximal to the framework. The conformation of the remaining residues of loops longer than 10 residues can also be predicted in many cases. This, combined with the previously defined canonical structures for the other five hypervariable loops, is an important step toward the prediction of the complete immunoglobulin antigen-binding site. We exemplify our prediction protocol using three known immunoglobulin structures as test cases.
Similar articles
- Conformations of the third hypervariable region in the VH domain of immunoglobulins.
Morea V, Tramontano A, Rustici M, Chothia C, Lesk AM. Morea V, et al. J Mol Biol. 1998 Jan 16;275(2):269-94. doi: 10.1006/jmbi.1997.1442. J Mol Biol. 1998. PMID: 9466909 - Framework residue 71 is a major determinant of the position and conformation of the second hypervariable region in the VH domains of immunoglobulins.
Tramontano A, Chothia C, Lesk AM. Tramontano A, et al. J Mol Biol. 1990 Sep 5;215(1):175-82. doi: 10.1016/S0022-2836(05)80102-0. J Mol Biol. 1990. PMID: 2118959 - Standard conformations for the canonical structures of immunoglobulins.
Al-Lazikani B, Lesk AM, Chothia C. Al-Lazikani B, et al. J Mol Biol. 1997 Nov 7;273(4):927-48. doi: 10.1006/jmbi.1997.1354. J Mol Biol. 1997. PMID: 9367782 - Conformations of immunoglobulin hypervariable regions.
Chothia C, Lesk AM, Tramontano A, Levitt M, Smith-Gill SJ, Air G, Sheriff S, Padlan EA, Davies D, Tulip WR, et al. Chothia C, et al. Nature. 1989 Dec 21-28;342(6252):877-83. doi: 10.1038/342877a0. Nature. 1989. PMID: 2687698 Review. - [Molecular modeling of immunological proteins by bioinformatics].
Nakamura H. Nakamura H. Nihon Rinsho. 1998 Mar;56(3):795-802. Nihon Rinsho. 1998. PMID: 9549375 Review. Japanese.
Cited by
- Physicochemical differences between camelid single-domain antibodies and mammalian antibodies.
Eskier NE, Eskier D, Firuzan E, Uzunlar SK. Eskier NE, et al. Turk J Biol. 2023 Dec 7;47(6):423-436. doi: 10.55730/1300-0152.2676. eCollection 2023. Turk J Biol. 2023. PMID: 38681780 Free PMC article. - VHH Structural Modelling Approaches: A Critical Review.
Vishwakarma P, Vattekatte AM, Shinada N, Diharce J, Martins C, Cadet F, Gardebien F, Etchebest C, Nadaradjane AA, de Brevern AG. Vishwakarma P, et al. Int J Mol Sci. 2022 Mar 28;23(7):3721. doi: 10.3390/ijms23073721. Int J Mol Sci. 2022. PMID: 35409081 Free PMC article. Review. - Conformational Ensembles of Antibodies Determine Their Hydrophobicity.
Waibl F, Fernández-Quintero ML, Kamenik AS, Kraml J, Hofer F, Kettenberger H, Georges G, Liedl KR. Waibl F, et al. Biophys J. 2021 Jan 5;120(1):143-157. doi: 10.1016/j.bpj.2020.11.010. Epub 2020 Nov 18. Biophys J. 2021. PMID: 33220303 Free PMC article. - Phage Display Libraries for Antibody Therapeutic Discovery and Development.
Almagro JC, Pedraza-Escalona M, Arrieta HI, Pérez-Tapia SM. Almagro JC, et al. Antibodies (Basel). 2019 Aug 23;8(3):44. doi: 10.3390/antib8030044. Antibodies (Basel). 2019. PMID: 31544850 Free PMC article. Review. - Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates.
Dostalek M, Prueksaritanont T, Kelley RF. Dostalek M, et al. MAbs. 2017 Jul;9(5):756-766. doi: 10.1080/19420862.2017.1323160. Epub 2017 May 2. MAbs. 2017. PMID: 28463063 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources