References
- Marsh JA, Teichmann SA, Forman-Kay JD. Probing the diverse landscape of protein flexibility and binding. Curr Opin Struct Biol. 2012;22(5):643–13. doi:https://doi.org/10.1016/j.sbi.2012.08.008.
- Koshland DE. Enzyme flexibility and enzyme action. J Cell Comp Physiol. 1959;54(S1):245–58. doi:https://doi.org/10.1002/jcp.1030540420.
- Eisenmesser EZ, Millet O, Labeikovsky W, Korzhnev DM, Wolf-Watz M, Bosco DA, Skalicky JJ, Kay LE, Kern D. Intrinsic dynamics of an enzyme underlies catalysis. Nature. 2005;438(7064):117–21. doi:https://doi.org/10.1038/nature04105.
- Kamerzell TJ, Middaugh CR. The complex inter-relationships between protein flexibility and stability. J Pharm Sci. 2008;97(9):3494–517. doi:https://doi.org/10.1002/jps.21269.
- Frauenfelder H, Sligar SG, Wolynes PG. The energy landscapes and motions of proteins. Science. 1991;254(5038):1598–603. doi:https://doi.org/10.1126/science.1749933.
- Henzler-Wildman K, Kern D. Dynamic personalities of proteins. Nature. 2007;450(7172):964–72. doi:https://doi.org/10.1038/nature06522.
- Bonomi M, Vendruscolo M. Determination of protein structural ensembles using cryo-electron microscopy. Curr Opin Struct Biol. 2019;56:37–45. doi:https://doi.org/10.1016/j.sbi.2018.10.006.
- Van Den Bedem H, Fraser JS. Integrative, dynamic structural biology at atomic resolution - It’s about time. Nat Methods. 2015;12(4):307–18. doi:https://doi.org/10.1038/nmeth.3324.
- Bonomi M, Heller GT, Camilloni C, Vendruscolo M. Principles of protein structural ensemble determination. Curr Opin Struct Biol. 2017;42:106–16. doi:https://doi.org/10.1016/j.sbi.2016.12.004.
- Berkowitz SA, Houde DJ. The complexity of protein structure and the challenges it poses in developing biopharmaceuticals. In Houde DJ, Berkowitz SA, editors. Biophysical characterization of proteins in developing biopharmaceuticals. MA: Elsevier; 2014. 1–21.
- Rabia LA, Desai AA, Jhajj HS, Tessier PM. Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility. Biochem Eng J. 2018;137:365–74. doi:https://doi.org/10.1016/j.bej.2018.06.003.
- Manikwar P, Majumdar R, Hickey JM, Thakkar SV, Samra HS, Sathish HA, Bishop SM, Middaugh CR, Weis DD, Volkin DB. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry. J Pharm Sci. 2013;102(7):2136–51. doi:https://doi.org/10.1002/jps.23543.
- Ewert S, Huber T, Honegger A, Plückthun A. Biophysical properties of human antibody variable domains. J Mol Biol. 2003;325(3):531–53. doi:https://doi.org/10.1016/S0022-2836(02)01237-8.
- Wang X, Das TK, Singh SK, Kumar S. Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies. mAbs. 2009;1(3):254–67. doi:https://doi.org/10.4161/mabs.1.3.8035.
- Wu TT, Johnson G, Kabat EA. Length distribution of CDRH3 in antibodies. Proteins: Structure, Function, and Bioinformatics. 1993;16(1):1–7. doi:https://doi.org/10.1002/prot.340160102.
- Weitzner BD, Dunbrack RL, Gray JJ. The origin of CDR H3 structural diversity. Structure. 2015;23(2):302–11. doi:https://doi.org/10.1016/j.str.2014.11.010.
- Marks C, Deane CM. Antibody H3 structure prediction. Comput Struct Biotechnol J. 2017;15:222–31. doi:https://doi.org/10.1016/j.csbj.2017.01.010.
- Koshland DE. Application of a theory of enzyme specificity to protein synthesis. Proceedings National Academy of Sci. 1958;44(2):98–104. doi:https://doi.org/10.1073/pnas.44.2.98.
- Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol. 1965;12(1):88–118. doi:https://doi.org/10.1016/S0022-2836(65)80285-6.
- Changeux J-P, Edelstein S. Conformational selection or induced fit? 50 years of debate resolved. F1000 Biol Rep. 2011;3:19–19. doi:https://doi.org/10.3410/B3-19.
- Boehr DD, Nussinov R, Wright PE. The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol. 2009;5(11):789–96. doi:https://doi.org/10.1038/nchembio.232.
- Fernández-Quintero ML, Kraml J, Georges G, Liedl KR. CDR-H3 loop ensemble in solution – conformational selection upon antibody binding. mAbs. 2019;11(6):1077–88. doi:https://doi.org/10.1080/19420862.2019.1618676.
- Kondrashov DA, Roberts SA, Weichsel A, Montfort WR. Protein functional cycle viewed at atomic resolution: conformational change and mobility in nitrophorin 4 as a function of pH and NO binding. Biochemistry. 2004;43(43):13637–47. doi:https://doi.org/10.1021/bi0483155.
- Menyhárd DK, Keserü GM. Protonation state of Asp30 exerts crucial influence over surface loop rearrangements responsible for NO release in nitrophorin 4. FEBS Lett. 2005;579(24):5392–98. doi:https://doi.org/10.1016/j.febslet.2005.09.003.
- Di Russo NV, Estrin DA, Martí MA, Roitberg AE. pH-dependent conformational changes in proteins and their effect on experimental pkas: the case of nitrophorin 4. PLoS Comput Biol. 2012;8(11). doi:https://doi.org/10.1371/journal.pcbi.1002761.
- Chennamsettya NV, Kaysera V, Helkb, B V, Trouta BL. Design of therapeutic proteins with enhanced stability.pdf. PNAS. 2009;106:11937–42.
- Chung S, Tian J, Tan Z, Chen J, Zhang N, Huang Y, Vandermark E, Lee J, Borys M, Li ZJ. Modulating cell culture oxidative stress reduces protein glycation and acidic charge variant formation. mAbs. 2019;11(1):205–16. doi:https://doi.org/10.1080/19420862.2018.1537533.
- Liu H, Nowak C, Shao M, Ponniah G, Neill A. Impact of cell culture on recombinant monoclonal antibody product heterogeneity. Biotechnol Prog. 2016;32(5):1103–12. doi:https://doi.org/10.1002/btpr.2327.
- Vlasak J, Ionescu R. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods. Curr Pharm Biotechnol. 2008;9(6):468–81. doi:https://doi.org/10.2174/138920108786786402.
- Du Y, Walsh A, Ehrick R, Xu W, May K, Liu H. Chromatographic analysis of the acidic and basic species of recombinant monoclonal antibodies. mAbs. 2012;4(5):578–85. doi:https://doi.org/10.4161/mabs.21328.
- Chumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;850(1–2):285–94. doi:https://doi.org/10.1016/j.jchromb.2006.11.050.
- Teshima G, Li MX, Danishmand R, Obi C, To R, Huang C, Kung J, Lahidji V, Freeberg J, Thorner L, et al. Separation of oxidized variants of a monoclonal antibody by anion-exchange. J Chromatogr A. 2011;1218(15):2091–97. doi:https://doi.org/10.1016/j.chroma.2010.10.107.
- Yan B, Steen S, Hambly D, Valliere-Douglass J, Vanden Bos T, Smallwood S, Yates Z, Arroll T, Han Y, Gadgil H, et al. Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain. J Pharm Sci. 2009;98(10):3509–21. doi:https://doi.org/10.1002/jps.21655.
- Kimerer LK, Pabst TM, Hunter AK, Carta G. Chromatographic behavior of bivalent bispecific antibodies on cation exchange columns. I. Experimental observations and phenomenological model. J Chromatogr A. 2019 Sept.13;1801:121–231. doi:https://doi.org/10.1016/j.chroma.2019.04.012.
- Ponniah G, Nowak C, Neill A, Liu H. Characterization of charge variants of a monoclonal antibody using weak anion exchange chromatography at subunit levels. Anal Biochem. 2017;520:49–57. doi:https://doi.org/10.1016/j.ab.2016.12.017.
- Harris RJ, Kabakoff B, Macchi FD, Shen FJ, Kwong M, Andya JD, Shire SJ, Bjork N, Totpal K, Chen AB. Identification of multiple sources of charge heterogeneity in a recombinant antibody. J Chromatogr B Biomed Sci Appl. 2001;752(2):233–45. doi:https://doi.org/10.1016/S0378-4347(00)00548-X.
- Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, Kirchmeier M, Corvaïa N, Ionescu R, Beck A. Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Anal Biochem. 2009;392(2):145–54. doi:https://doi.org/10.1016/j.ab.2009.05.043.
- Perkins M, Theiler R, Lunte S, Jeschke M. Determination of the origin of charge heterogeneity in a murine monoclonal antibody. Pharm Res. 2000;17(9):1110–17. doi:https://doi.org/10.1023/A:1026461830617.
- Sreedhara A, Cordoba A, Zhu Q, Kwong J, Liu J. Characterization of the isomerization products of aspartate residues at two different sites in a monoclonal antibody. Pharm Res. 2012;29(1):187–97. doi:https://doi.org/10.1007/s11095-011-0534-2.
- Zhang Z, Zhou S, Han L, Zhang Q, Pritts WA. Impact of linker-drug on ion exchange chromatography separation of antibody-drug conjugates. mAbs. 2019;11(6):1113–21. doi:https://doi.org/10.1080/19420862.2019.1628589.
- Kopaciewicz W, Rounds MA, Fausnaugh J, Regnier FE. Retention model for high-performance ion-exchange chromatography. J Chromatogr A. 1983;266(C):3–21. doi:https://doi.org/10.1016/S0021-9673(01)90875-1.
- Regnier FE. The role of protein structure in chromatographic behavior. Science. 1987;238(4825):319–23. doi:https://doi.org/10.1126/science.3310233.
- Luo H, Cao M, Newell K, Afdahl C, Wang J, Wang WK, Li Y. Double-peak elution profile of a monoclonal antibody in cation exchange chromatography is caused by histidine-protonation-based charge variants. J Chromatogr A. 2015;1424:92–101. doi:https://doi.org/10.1016/j.chroma.2015.11.008.
- Luo H, Macapagal N, Newell K, Man A, Parupudi A, Li Y, Li Y. Effects of salt-induced reversible self-association on the elution behavior of a monoclonal antibody in cation exchange chromatography. J Chromatogr A. 2014;1362:186–93. doi:https://doi.org/10.1016/j.chroma.2014.08.048.
- Guo J, Creasy AD, Barker G, Carta G. Surface induced three-peak elution behavior of a monoclonal antibody during cation exchange chromatography. J Chromatogr A. 2016;1474:85–94. doi:https://doi.org/10.1016/j.chroma.2016.10.061.
- Masiero A, Nelly L, Marianne G, Christophe S, Florian L, Ronan C, Claire B, Cornelia Z, Grégoire B, Eric L, et al. The impact of proline isomerization on antigen binding and the analytical profile of a trispecific anti-HIV antibody. mAbs. 2020;12:1. doi:https://doi.org/10.1080/19420862.2019.1698128.
- Hallgren E, Kálmán F, Farnan D, Horváth C, Ståhlberg J. Protein retention in ion-exchange chromatography: effect of net charge and charge distribution. J Chromatogr A. 2000;877(1–2):13–24. doi:https://doi.org/10.1016/S0021-9673(00)00190-4.
- Yu L, Zhang L, Sun Y. Protein behavior at surfaces: orientation, conformational transitions and transport. J Chromatogr A. 2015;1382:118–34. doi:https://doi.org/10.1016/j.chroma.2014.12.087.
- Kittelmann J, Lang KMH, Ottens M, Hubbuch J. Orientation of monoclonal antibodies in ion-exchange chromatography: a predictive quantitative structure–activity relationship modeling approach. J Chromatogr A. 2017;1510:33–39. doi:https://doi.org/10.1016/j.chroma.2017.06.047.
- Chung WK, Hou Y, Freed A, Holstein M, Makhatadze GI, Cramer SM. Investigation of protein binding affinity and preferred orientations in ion exchange systems using a homologous protein library. Biotechnol Bioeng. 2009;102(3):869–81. doi:https://doi.org/10.1002/bit.22100.
- Diepold K, Bomans K, Wiedmann M, Zimmermann B, Petzold A, Schlothauer T, Mueller R, Moritz B, Stracke JO, Mølhøj M, et al. Simultaneous assessment of asp isomerization and asn deamidation in recombinant antibodies by LC-MS following incubation at elevated temperatures. PLoS One. 2012;7(1):e30295. doi:https://doi.org/10.1371/journal.pone.0030295.
- Eakin CM, Miller A, Kerr J, Kung J, Wallace A. Assessing analytical methods to monitor isoAsp formation in monoclonal antibodies. Front Pharmacol. 2014;5:87. doi:https://doi.org/10.3389/fphar.2014.00087.
- Lu X, Nobrega RP, Lynaugh H, Jain T, Barlow K, Boland T, Sivasubramanian A, Vasquez M, Xu Y. Deamidation and isomerization liability analysis of 131 clinical-stage antibodies. MAbs. 2019;11(1):45–57. doi:https://doi.org/10.1080/19420862.2018.1548233.
- Stephenson RC, Clarke S. Succinimide formation from aspartyl and asparaginpyelp tides as a model for the spontaneous degradation of proteins. J Biologiclhem. 1989;264(11):6411–70.
- Tanford C, Bunville LG, Nozaki Y. The Reversible Transformation of β-Lactoglobulin at pH 7.5. J Am Chem Soc. 1959;81(15):4032–36. doi:https://doi.org/10.1021/ja01524a054.
- Tanford C, Taggart VG. Ionization-linked changes in protein conformation. II. The N → R transition in β-lactoglobulin. J Am Chem Soc. 1961;83:1634–38.
- Tanford C. Ionization-linked changes in protein conformation. I. Theory. J Am Chem Soc. 1961;83(7):1628–34. doi:https://doi.org/10.1021/ja01468a021.
- Brownlow S, Morais Cabral JH, Cooper R, Flower DR, Yewdall SJ, Polikarpov I, North ACT, Sawyer L. Bovine β-lactoglobulin at 1.8 Å resolution - Still an enigmatic lipocalin. Structure. 1997;5(4):481–95. doi:https://doi.org/10.1016/S0969-2126(97)00205-0.
- Qin BY, Bewley MC, Creamer LK, Baker HM, Baker EN, Jameson GB. Structural basis of the tanford transition of bovine β-lactoglobulin. Biochemistry. 1998;37(40):14014–23. doi:https://doi.org/10.1021/bi981016t.
- Weichsel A, Andersen JF, Roberts SA, Montfort WR. Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial. Nat Struct Biol. 2000;7(7):551–54. doi:https://doi.org/10.1038/76769.
- Roche S, Bressanelli S, Rey FA, Gaudin Y. Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science. 2006;313(5784):187–91. doi:https://doi.org/10.1126/science.1127683.
- Stampfer SD, Lou H, Cohen GH, Eisenberg RJ, Heldwein EE. Structural basis of local, pH-dependent conformational changes in glycoprotein B from herpes simplex virus type 1. J Virol. 2010;84(24):12924–33. doi:https://doi.org/10.1128/JVI.01750-10.
- Zubkov S, Gronenborn AM, Byeon IJL, Mohanty S. Structural consequences of the pH-induced conformational switch in A. polyphemus pheromone-binding protein: mechanisms of ligand release. J Mol Biol. 2005;354:1081–90.
- Harms MJ, Castañeda CA, Schlessman JL, Sue GR, Isom DG, Cannon BR, García-Moreno E,B. The pKa values of acidic and basic residues buried at the same internal location in a protein are governed by different factors. J Mol Biol. 2009;389:34–47.
- Isom DG, Cannon BR, Castañeda CA, Robinson A, García-Moreno E,B. High tolerance for ionizable residues in the hydrophobic interior of proteins. Proc Natl Acad Sci U S A. 2008;105(46):17784–88. doi:https://doi.org/10.1073/pnas.0805113105.
- Isom DG, Castañed CA, Cannon BR, García-Moreno BE. Large shifts in pKa values of lysine residues buried inside a protein. Proc Natl Acad Sci U S A. 2011;108(13):5260–65. doi:https://doi.org/10.1073/pnas.1010750108.
- Isom DG, Castañeda CA, Cannon BR, Velu PD, García-Moreno E,B. Charges in the hydrophobic interior of proteins. Proc Natl Acad Sci U S A. 2010;107(37):16096–100. doi:https://doi.org/10.1073/pnas.1004213107.
- Jorgensen WL,CJ, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79:926–35. doi:https://doi.org/10.1063/1.445869.
- Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K. Scalable molecular dynamics with NAMD. J Comput Chem. 2005;26(16):1781–802. doi:https://doi.org/10.1002/jcc.20289.