تحليل الحلقات شديدة التغير يفسر محددات تسلسل استقرار الأجسام المضادة.

Key Points

• This research investigates how sequences in complementarity-determining regions affect the stability of antibodies.
• Developed a high-throughput deep loop profiling method to assess folding fitness across millions of diverse CDRs.
• Utilized machine learning models trained on extensive data to predict folding propensity from the CDR sequences.
• Employed the insights gained to stabilize specific unstable nanobodies.
• Identified key folding determinants in CDR1 and CDR2 that influence antibody stability.
• Rescued two unstable nanobodies, improving their stability and folding competence.
• Created synthetic libraries of nanobodies with enhanced biophysical properties.