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Principal Scientist (Structural Biology)

Alameda, California, US
Closing date
Sep 19, 2023

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Academic / Research
Conservation science
Salary Type
Employment Type
Full time

We are seeking a highly skilled and motivated structural biologist to join and help build a world class structural biology team. The successful candidate will have hands on practical experience in supporting structure-based drug design (SBDD) for small molecule discovery projects. Specifically, this candidate must have a demonstrated track record of contributing to the design of small molecule modulators using modern SBDD and computational assisted drug discovery (CADD) methods, since this is a major focus for the role. The successful candidate will have a strong background in biochemistry and/or biophysics and, in addition to supporting SBDD, is expected to impact discovery teams through the conceptualization, design, and execution of key experiments and reagents. Strong communication and collaboration skills are essential since this position will interact extensively across discovery departments and teams.

  • Proficient in the structural analysis of small molecule-protein complexes by X-ray crystallography and/or cryo-electron microscopy (cryo-EM)
  • Skilled in structure-based drug design (SBDD) and strong familiarity with diverse computational assisted drug discovery (CADD) methods
  • Experience in the design and optimization of small molecules for hit-to-lead and lead optimization project stages in collaboration with medicinal chemists and computational chemists
  • Expanding knowledge of medicinal chemistry, multi-parameter optimization, and ADMET concepts
  • Purify, prepare, and optimize samples of diverse small molecule-protein complexes for X-ray and/or cryo-EM structural analysis
  • Routinely present results to medicinal chemists, computational chemists, and project teams highlighting avenues to improve small molecule potency, selectivity, and other desired properties through modern SBDD/CADD methods
  • Evaluate established or new technologies to help advance protein production, structural determination and/or ligand discovery and characterization capabilities
  • Maintain laboratory notebooks in accordance with company policies and practices
  • Comply with safe laboratory practices and EH&S guidelines
  • Contribute to the writing of technical documents, patents, scientific manuscripts, etc.


  • PhD degree in structural biology, biophysics, computational drug design or related discipline and a minimum of five (5) years of related industry experience; or,
  • Master's degree in structural biology, biophysics, computational drug design or related discipline and a minimum of nine (9) years of related experience; or,
  • Bachelor's degree in structural biology, biophysics, computational drug design or related discipline and a minimum of eleven (11) years of related experience; or,
  • Equivalent combination of education and experience.

  • Experience in small molecule structure-based drug design (SBDD) is essential
  • At least 3-5 years of relevant industry experience directly supporting active medicinal chemistry projects through SBDD is strongly preferred
  • Strong expertise in the expression, purification, optimization, and structural analysis of diverse and challenging protein targets by X-ray crystallography and/or cryo-EM is required
  • Experience with biophysical techniques (SEC-MALS, DSF, SPR, Octet, etc.) for assessing the stability, solubility, and oligomerization status of proteins and ligand interactions is required
  • Research accomplishments demonstrated by strong publication and/or patent record

  • X-ray structure determination by molecular replacement and experimental phasing
  • Experience optimizing samples and analyzing data by single particle cryo-EM
  • Expertise in the design, expression, and purification of multiple classes of protein targets to support successful structure determination (experience with kinases, multi-protein complexes, E3 ligases, transcription factors is a plus)
  • Sustained experience with structure-based drug design strategies and software packages
  • Strong familiarity with medicinal chemistry, computational chemistry, computational structural biology methods, bioinformatic analysis and/or programming skills is a plus
  • Ability to build and manage productive collaborations with cross-functional project teams and CROs is essential
  • Ability to multi-task in a fast-paced dynamic environment while delivering high-quality work is essential
  • Excellent interpersonal, written, and verbal communication skills is essential


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 severalU.S. geographic markets, and we pay differently based on those defined markets. The base pay range for this positionis $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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