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International Journal of Molecular Biotechnological Research Review Article

Integrative Structural-Functional Genomics of Fc and Fab: Precision Models for Monoclonal Antibody Stability and Anti-Aggregation Engineering

  1. Tapaswi Ram Khajuria Education Dept. Govt. Higher Sec School Barola Udhampur
  2. Prof (Dr.) Atul Khajuria University School of Allied and Health Care Sciences Rayat Bahra Professional University VPO BOHAN, Tehsil Distt. Hoshiarpur
  3. KIRAN KUMARI Education Dept. Govt. High School Pachote, Chenani, Udhampur

Abstract

Monoclonal antibodies (mAbs) represent the cornerstone of biotherapeutics, yet aggregation propensity compromises up to 50% of candidates during development, driven by Fab hypervariability and Fc vulnerabilities.(1,2) This review integrates functional genomics from OAS (4B+ sequences)(5) and structural databases (SAbDab: 10K+ structures)(6) with machine learning models achieving R=0.97 for SAP prediction.(11) We dissect biophysical mechanisms, benchmark predictive tools (DeepSP, ESM2), and engineering strategies (YTE, FW mutations) that enhance Tm by 5-10°C while preserving affinity.(14,25) Case studies from trastuzumab variants and COVID mAbs demonstrate 30-55% aggregation reduction.(7,11) Integrative pipelines fuse repertoire mining, AlphaFold3 structures, and MD- featurized ML to de-risk developability, slashing attrition by 35%.(7) Future directions emphasize multi- task models for high-conc. subcutaneous delivery (200 mg/mL).(22)

Keywords

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