Job description

Principal Scientist, Computational Chemistry


Exelixis is dedicated to build a world-class Structure-Based Drug Design group to accelerate the discovery and development of novel therapeutics to fight cancer. We are seeking a highly experienced Computational Chemistry team member to help discover transformative medicines. 

The ideal candidate will have extensive expertise in ligand-based and structure-based drug design methods and will have contributed to the advancement of small molecule projects through all stages of drug discovery.  Of particular importance is the ability to build strong collaborations with medicinal chemists and structural biologists to help advance the drug discovery portfolio. Strong communication and collaboration skills are essential, as this position will interact closely with interdisciplinary small molecule discovery project teams. The successful candidate will help to build our Computational Chemistry capabilities and will collaborate with and support Medicinal Chemistry, Structural Biology, Bioinformatics and Discovery Sciences departments.


  • Help to define a robust strategy to integrate advanced computational chemistry and structure-based drug design methods into small molecule drug discovery programs
  • Help to build, integrate and apply computational tools and workflows to accelerate hit identification, hit-to-lead optimization, and candidate selection
  • Apply state-of-the-art structure-based drug design technologies to drive hit identification, lead optimization and candidate selection in close partnership with medicinal chemists and structural biologists
  • Expertise with ligand-based methods, QSAR, conformational analysis, physical chemical property modeling, molecular dynamics, free energy perturbation, molecular and quantum mechanics
  • Solid understanding of medicinal chemistry, in vitro and in vivo ADME, and ability to couple computational-driven approaches to drive lead optimization beyond potency
  • Strong understanding of the computational & informatics infrastructure required to support a robust SBDD/CADD capability
  • Provide day-to-day scientific leadership and project support and help to build a high-performing computational drug discovery capability
  • Conduct scientific presentations to senior management, project teams, and internal/external collaborators


  • Help to build and hire a team of computational chemists.


  • Ph.D. in computational chemistry, biophysics, physical organic chemistry, physics-based modeling, statistical modeling, ML/AI, mathematical modeling, or a related field with a clear track record of applying computational technologies and structure-based drug design to advance the discovery of small molecule therapeutics, and a minimum of 5 years of post-PhD experience; or,
  • M.Sc., as above, and a minimum of 9 years of post-degree experience; or,
  • B.Sc., as above, and minimum of 11 years of post-degree experience; or,
  • Equivalent combination of education and experience.


  • Experience with multiple drug target classes, orthosteric and allosteric binders, fragment-based screening and optimization, covalent binders, protein degraders and/or molecular glues is strongly preferred
  • Experience with machine learning/AI to rationalize SAR and recommend new molecules to test actionable hypotheses; ability to build predictive ML/AI-based models to improve potency, selectivity & ADME properties is strongly preferred
  • Strong experience in cheminformatics and knowledge of computing infrastructure is a plus
  • Background in library design, diversity analysis, and approaches to improve virtual screening, fragment, DEL and cell-based HTS is strongly preferred 
  • Working experience with software from companies such as Chemical Computing Group, Schrodinger, OpenEye, Dotmatics, Gaussian, Molsof, Chemaxon, Knime, RDKit and ICM Molsoft
  • Technical leader who stays on the cutting edge to identify emerging science to advance computational platforms
  • Demonstrated independent thought and creativity in science, and successful track-record in drug discovery as evidenced by patents, publications and invited presentations
  • Strong written, oral and presentation communication skills


If you like wild growth and working with happy, enthusiastic over-achievers, you'll enjoy your career with us!

Our compensation reflects the cost of labor across several U.S. geographic markets, and we pay differently based on those defined markets. The base pay range for this position is $131,500 - $195,500 annually. The base pay range may take into account the candidate’s geographic region, which will adjust the pay depending on the specific work location. The base pay offered will take into account the candidate’s geographic region, job-related knowledge, skills, experience and internal equity, among other factors.

In addition to the base salary, as part of our Total Rewards program, Exelixis offers comprehensive employee benefits package, including a 401k plan with generous company contributions, group medical, dental and vision coverage, life and disability insurance, and flexible spending accounts. Employees are also eligible for a discretionary annual bonus program, or if field sales staff, a sales-based incentive plan. Exelixis also offers employees the opportunity to purchase company stock, and receive long-term incentives, 15 accrued vacation days in their first year, 17 paid holidays including a company-wide winter shutdown in December, and up to 10 sick days throughout the calendar year.

The preceding job description has been designed to indicate the general nature and level of work performed by employees within this classification.  It is not designed to contain or be interpreted as a comprehensive inventory of all duties, responsibilities and qualifications required of employees assigned to the job.

We are an Equal Opportunity Employer and do not discriminate against any employee or applicant for employment because of race, color, sex, age, national origin, religion, sexual orientation, gender identity, status as a veteran, and basis of disability or any other federal, state or local protected class.

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