Senior / Principal Scientist, Molecular Simulations

The posting, as Flagship Pioneering, Inc. wrote it

About the Role

FL117 , a venture-backed stealth AI x bio company, is seeking a Sr. Scientist / Principal Scientist, Molecular Simulations . Here you will build the physics layer of a drug development AI platform. You will characterize how binders engage their targets and validate generated designs before they are committed to synthesis. You will work at the interface of structure-based modeling and generative ML, turning simulation output into training signals. We are looking for a hands-on simulation scientist who is comfortable owning a method end to end in a cross-functional, fast-moving team.

Responsibilities

• Binder Characterization : Run and interpret structural and dynamic analysis of ligand–target complexes peptides, macrocycles, nanobodies/VHHs, antibody CDRs.
• Pocket & Target Assessment : Characterize binding sites, including cryptic and induced-fit pockets, across the target portfolio using MD, enhanced sampling, and pocket detection methods.
• Design Validation : Triage generated molecules before synthesis through a combination of pose prediction and refinement, docking rescoring, binding-mode stability under MD, ligand strain and conformational ensemble analysis, and define the criteria by which a design advances or gets killed.
• Free Energy & Affinity Prediction : Build, validate, and own the affinity prediction workflow (relative and absolute FEP, MM-GBSA/PBSA, endpoint methods); establish its accuracy and applicability domain against measured data and report both honestly.
• Beyond-Rule-of-5 Properties : Model conformational behavior, intramolecular hydrogen bonding, chameleonicity, and membrane partitioning for macrocycles and other non-classical chemotypes to support oral property design.
• Simulation-to-ML Interface : Convert simulation output into structured signal for the generative platform in close partnership with the AI/ML team.
• Infrastructure & Throughput : Build reproducible, automated simulation pipelines on GPU cloud or HPC infrastructure; own system setup, parameterization, QC, and analysis at portfolio scale rather than one system at a time.
• Cross-functional Partnership : Work directly with medicinal chemistry, pharmacology, and external structural biology and assay partners; turn structural hypotheses into testable designs, feed returning data back into corrected models, and flag clearly where predictions are unreliable.

Must-have Qualifications

• PhD in computational chemistry, biophysics, chemical physics, structural biology, or a related field; MSc with equivalent industry depth considered
• 4+ years of post-PhD molecular simulation experience, at least part of it in a drug discovery setting (Sr. Scientist); 6+ years with demonstrated ownership of a method or platform (Principal)
• Deep hands-on expertise in classical molecular dynamics: force fields and small molecule parameterization (AMBER/CHARMM/OPLS, GAFF/OpenFF), solvation and ion treatment, equilibration protocols, and the cha

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The salary range for this role is $146,000 - $236,500. Compensation for the role will depend on a number of factors, including a candidate’s qualifications, skills, competencies, and experience. FL117 currently offers healthcare coverage, annual incentive program, retirement benefits and a broad range of other benefits. Compensation and benefits information is based on FL117's good faith estimate as of the date of publication and may be modified in the future.

Privacy Notice for Applicants: When you apply for a role at Flagship Pioneering or one of its portfolio companies, we collect and use personal information you provide (such as your name, contact details, work history, and application materials) to evaluate your application, communicate with you, and comply with legal obligations. Your application data is processed through Greenhouse, our applicant tracking system, and may also be reviewed using AI-assisted screening tools. We do not sell your personal information. California residents have rights under the CCPA/CPRA including to know, delete, and opt out of the sharing of their personal information. If you are located in the EU or UK, we process your data under GDPR and you have rights to access, rectify, and erase your data. To exercise your rights or for questions, contact privacy@flagshippioneering.com.