Senior / Principal Scientist, Structural Biology — Target Druggability & Structure-Based Drug Design

Schrödinger; New York (NY); On-site; USD 135,000 - 190,000; Full time

Benefits offered by this job

Stock options

Healthcare (dental/vision)

401k

Pre-tax commuter benefits

Flexible work schedule

Parental leave

Catered meals

Paid vacation

Job summary

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!

You’ll partner with multidisciplinary teams to define target tractability strategies, identify novel binding sites, and design experimental campaigns to solve structures that unlock challenging targets, bridging computation and experiment.

Qualifications

• PhD (or equivalent industrial experience) in Structural Biology, Biophysics, Computational Chemistry, or related discipline.
• Deep, hands-on expertise in structure-based drug design with practical experience in cryptic/transient binding site identification and pocket druggability assessment.
• Working fluency in modern computational structural biology methods such as AI-based structure prediction and MD-based sampling.
• Direct experience designing, executing, and interpreting cryo-EM and/or X-ray crystallography experiments.

Responsibilities

• 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, pocket identification and conformational sampling.
• Translate insights into actionable hypotheses for medicinal chemistry and biology teams and propose experiments to test them.
• Evaluate and integrate emerging methods into practical workflows.
• Present tractability assessments to project teams and leadership with clear rationale.
• Lead experimental structural biology efforts and manage external CROs or internal labs to enable drug discovery.
• Contribute to Schrödinger's platform strategy by feeding tractability-driven requirements back to software development.

Skills

PhD in Structural Biology

Structure-based drug design

AI/ML for structure prediction

Cryo-EM / X-ray crystallography

Platform familiarity (Schrödinger)

Education

PhD in Structural Biology

Tools

Schrödinger platform (Glide, FEP+, BioLuminate, Prime)

Cryo-EM

X-ray crystallography

Job description

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!

Schrödinger has pioneered a physics-based software platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The software platform is used by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Our multidisciplinary drug discovery team also leverages the software platform to advance collaborative programs and its own pipeline of novel therapeutics to address unmet medical needs.As a member of our Structural Biology and Target Enablement team in our Therapeutics Group, you’ll partner with Molecular Pharmacologists, Biologists, Medicinal Chemists, and Computational Chemists to define target tractability strategies, identify and validate novel and cryptic binding sites, and design and supervise experimental campaigns to solve unprecedented structures that unlock previously intractable targets. Sitting at the interface of computation and experiment, you’ll be as comfortable proposing in silico-predicted binding site hypotheses as you are designing and executing the experimental structural biology strategies to test them.

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 (or equivalent industrial experience) in Structural Biology, Biophysics, Computational Chemistry, 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

Pay And Perks

Schrödinger understands it’s people that make a company great. Because of this, we’re prepared to offer a competitive salary, stock options, and a wide range of benefits that include healthcare (with dental and vision), a 401k, pre‑tax commuter benefits, a flexible work schedule, and a parental leave program. We have catered meals in the office, a company culture that is relaxed but engaged, and over a month of paid vacation time.

Estimated base salary range: $135,000 - $190,000. Actual compensation package is dependent on a number of factors, including, for example, experience, education, degrees held, market data, and business needs.

As an equal opportunity employer, Schrödinger hires outstanding individuals into every position in the company. People who work with us have a high degree of engagement, a commitment to working effectively in teams, and a passion for the company's mission. We place the highest value on creating a safe environment where our employees can grow and contribute, and refuse to discriminate on the basis of race, color, religious belief, sex, age, disability, national origin, alienage or citizenship status, marital status, partnership status, caregiver status, sexual and reproductive health decisions, gender identity or expression, sexual orientation, or any other protected characteristic. To us, "diversity" isn't just a buzzword, but an important element of our core principles and key business practices. We believe that diverse companies innovate better and think more creatively than homogenous ones because they take into account a wide range of viewpoints. For us, greater diversity doesn't mean better headlines or public images - it means increased adaptability and profitability.