Melissa Rios Zertuche

About

Melissa Maria Rios Zertuche completed her MSc in Bioscience at KAUST in 2024 under the supervision of Robert Hoehndorf. Her thesis project was carried out in collaboration with the Eppinger lab and developed a computational pipeline for the rational design and optimisation of nanobodies.

Her thesis, Establishment and Evaluation of a Computational Workflow for the Design and Optimization of Nanobodies, addresses the lack of comprehensive end-to-end computational tools tailored to the design of single-domain antibodies. Nanobodies (VHHs) are roughly one-tenth the size of conventional antibodies, yet retain comparable binding affinity and offer markedly better stability, solubility, and production economics, which has made them increasingly attractive both as research tools and as therapeutics. State-of-the-art deep-learning methods can co-design sequence and structure of the heavy-chain complementarity-determining regions (CDRs), but they struggle in the de novo setting where no experimentally determined antigen–antibody complex is available.

The thesis assembles and evaluates a complete workflow integrating structure prediction, antibody–antigen docking, CDR generation, and side-chain packing, and investigates the propagation of error along this pipeline as well as filtering criteria to ensure that only intermediates of sufficient quality are passed to subsequent stages. The work bridges bioengineering, structural bioinformatics, and machine learning for protein design, and contributes to the group's collaborative activities with KAUST's bioscience and biomolecular engineering communities on antibody and nanobody engineering.