Principal Scientist, Computational Protein Design

Moderna Therapeutics; Cambridge (MA); On-site; USD 180,000 - 240,000; Full time

Job summary

Moderna Therapeutics in Cambridge, MA is seeking a Principal Scientist to lead computational protein design across therapeutic research, focusing on TCRs and antibodies and contributing to broader design efforts. The role requires deep expertise in protein structure, de novo binder design, molecular recognition, and state-of-the-art computational design workflows.

You will partner with structural biology, immunology, translational science, and program teams to advance platform innovation and

Qualifications

• Experience leading computational protein design campaigns for therapeutics.
• Focus on de novo binder design for TCRs and antibodies.
• Ability to build integrated computational-to-experimental design platforms.

Responsibilities

• Lead computational protein design campaigns for TCRs and antibodies.
• Develop binder optimization for affinity, specificity, stability, and developability.
• Build an integrated design platform linking generative design, docking, interface scoring, and sequencing.
• Collaborate with cross-functional teams to translate model outputs into experimental data.

Skills

Computational design

TCR design

Antibody design

Molecular modeling

Job description

The Role:

Moderna’s Therapeutics Research group is seeking a talented, experienced, and highly motivated Principal Scientist to support computational protein design across therapeutic research. This role will focus primarily on the design and optimization of T cell receptors and antibodies, while also contributing to broader protein design efforts across a range of therapeutic modalities. The successful candidate will bring deep expertise in protein structure, de novo binder design, molecular recognition, and state-of-the-art computational design methods and workflows. They will serve as a scientific and technical leader for computational binder design, helping to build a next-generation platform for the discovery, engineering, and optimization of TCRs and antibodies against defined targets. This individual will work in close partnership with structural biology, directed evolution, immunology, translational science, and program teams to advance platform innovation and therapeutic programs across Moderna's Research and Early Development portfolio.

Here’s What You’ll Do

Lead and execute computational protein design campaigns across therapeutic research, with a focus on de novo binder design for TCRs and antibodies. Drive computational binder optimization approaches to improve affinity, specificity, stability, expression, cognate pairing efficiency, potency, developability, sequence liabilities, and compatibility with mRNA-expressed therapeutic formats. Help build an integrated computational-to-experimental design platform that connects generative design, docking, interface scoring, rational library design, display or functional screening, next-generation sequencing, and active-learning cycles. Establish computational off-target screening strategies for engineered TCRs and other binders, including structural motif scanning, alloreactivity risk assessment, counterselection logic, and prioritization of candidates for experimental validation. Partner with cross-reactivity, microbial display, directed evolution, structural biology, functional assay, and program teams to convert model outputs into experimental data and incorporate assay results into iterative model improvement. Evaluate, deploy, and advance state-of-the-art computational methods, including structure prediction, inverse folding, diffusion-or flow-based generation, protein language models, molecular docking, molecular dynamics, interface scoring, and multi-objective optimization. Identify external technologies, datasets, software capabilities, and strategic partnerships that accelerate computational protein design workflows