Principal Scientist, Computational Protein Design (AI/ML)

Location: Cambridge, Massachusetts, United States. The role follows a 70/30 work model with 70% in-office collaboration. Only U.S. persons, including citizens, permanent residents, asylees, or refugees, are eligible due to U.S. export control requirements.

Salary: $142,500–$256,500 per year, plus potential bonus, incentive compensation, or equity.

Company

hirify.global develops mRNA-based therapeutics and vaccines across infectious diseases, immuno-oncology, rare diseases, and cardiovascular diseases.

What you will do

• Lead computational protein design campaigns focused on de novo TCR and antibody binder generation.
• Optimize binders for affinity, specificity, stability, expression, potency, developability, and compatibility with mRNA-expressed formats.
• Build computational-to-experimental design platforms integrating generative design, docking, interface scoring, library design, screening, sequencing, and active learning.
• Develop off-target, cross-reactivity, alloreactivity, and counterselection strategies for engineered TCRs and other binders.
• Partner with structural biology, directed evolution, immunology, translational science, assay, and program teams to improve models using experimental data.
• Evaluate advanced methods including structure prediction, inverse folding, diffusion- and flow-based generation, protein language models, molecular dynamics, and multi-objective optimization.

Requirements

• PhD in computational biology, protein engineering, bioinformatics, structural biology, biophysics, or a related discipline.
• At least 5 years of post-graduate experience in computational protein design, including AI/ML-guided and structure-informed de novo binder design.
• Experience connecting computational design with experimental validation and optimization workflows.
• Fluency with tools such as AlphaFold, AlphaFold-Multimer, Rosetta, PyRosetta, RFdiffusion, and ProteinMPNN.
• Experience mentoring scientists, managing at least one direct report, or providing scientific leadership.
• Eligibility as a U.S. person is required; the role cannot sponsor non-U.S. persons for an export control license.

Nice to have

• Direct experience with TCR design, TCR therapeutic engineering, HLA restriction, cross-reactivity, or alloreactivity.
• Experience with Python-based machine learning workflows and computational specificity, developability, or off-target screening.
• Familiarity with yeast, mammalian, or phage display; deep mutational scanning; binding assays; and cell-based functional assays.
• Experience designing enzymes, catalysts, DNA- or RNA-binding proteins, CAR signaling domains, scaffolds, switches, sensors, or intracellular proteins.

Culture & Benefits

• In-person collaboration supported by a 70/30 office-based work model.
• Competitive healthcare and voluntary benefit programs.
• Fitness, mindfulness, and mental health resources.
• Family planning benefits, including fertility, adoption, and surrogacy support.
• Paid vacation, volunteer days, sabbatical, global recharge days, and year-end shutdown.
• Savings and investment programs plus location-specific benefits.