Schrödinger seeks a Senior or Principal Scientist in Structural Biology (Target Druggability and Structure-Based Drug Design) to join us in our mission to transform the discovery of therapeutics and materials!

Who will love this job:

• A scientist with a track record of success in assessing and expanding oral drug tractability for challenging and undrugged targets
• A structural and computational biology expert who’s familiar with Schrödinger’s platform (Glide, FEP+, BioLuminate, Prime, etc.) or comparable structure-based design software
• A veteran of computational-experimental hybrid work in biotech, pharma, or an SBDD-focused software company
• A researcher who has worked on modality-switch programs (e.g., biologic-to-small-molecule or PROTAC/molecular glue strategies)
• An excellent scientific communicator who has presented target tractability assessments to senior stakeholders and defended hypotheses under scientific scrutiny

What you’ll do:

• Define druggability hypotheses for difficult-to-drug targets by integrating structural, computational, biophysical, and pharmacological evidence
• Apply and advance computational methods, including AI/ML approaches, for structure prediction and refinement, small-molecule binding site identification (including cryptic and transient pockets), pocket druggability scoring, and conformational sampling of target ensembles
• Translate structural and computational insights into actionable hypotheses for medicinal chemistry and biology teams, proposing specific experiments (biophysical, structural, or computational) to test and de-risk emerging druggability hypotheses
• Evaluate and integrate emerging methods (e.g., generative structure prediction, cryptic pocket detection, MD-based ensemble docking, AI-based binding site/ligandability prediction) into practical workflows
• Present target tractability assessments to project teams, portfolio review committees, and leadership, communicating complex structural/computational rationale clearly to non-specialist audiences
• Lead experimental structural biology efforts on active target enablement and drug discovery programs, managing work at external CROs, collaborating with our internal Structural Biology team, and/or directly performing hands-on experiments at our internal laboratory
• Contribute to Schrödinger's broader platform strategy, feeding practical, target-tractability-driven requirements back into internal software and methods development

What you should have:

• PhD in Structural Biology, Biophysics, or a related discipline
• Deep, hands-on expertise in structure-based drug design, including practical experience with cryptic/transient binding site identification and pocket druggability assessment
• Working fluency in modern computational structural biology methods, such as AI-based structure prediction, MD-based conformational sampling, binding site/pocket detection algorithms, and structure refinement
• Direct experience designing, executing, and interpreting cryo-EM and/or X-ray crystallography experiments, including strategies for capturing difficult, dynamic, or novel structural states