Senior Principal Scientist, Computational Chemistry, ADC Chemistry

ROLE SUMMARY

The ADC (Antibody Drug Conjugate) Chemistry group is seeking a highly motivated, creative, and experienced computational chemist with a proven track record of success in drug discovery, to develop novel payloads and linkers for antibody-drug conjugates (ADCs).

You will apply your background in drug development, medicinal chemistry, and computational chemistry to develop new anticancer therapies. Your background in structure-based drug discovery is critical for this position. You will work collaboratively within the chemistry department and researchers across the biology and translational sciences. You will play a vital role as scientific leader and key contributor to large, multi-disciplinary, matrix teams from project inception to delivery of clinical drug candidates.  

Our location is in Bothell, WA, near Seattle.  

The successful candidate will be responsible for identifying key opportunities for computational chemistry to impact drug discovery at all stages ranging from target evaluation to hit identification to lead optimization and candidate selection. You will also utilize your computational chemistry and scientific programming expertise to identify methods that can address key challenges and impact drug discovery across the portfolio.

The candidate should have good communication and organizational skills and have the ability to work in a flexible, dynamic team environment. As an independent researcher and leading member of project teams in Oncology, you will have opportunities to make numerous direct contributions to Pfizer's drug discovery efforts.

ROLE RESPONSIBILITIES:

• Structure Based Drug Design(SBDD) and conformational analysis is a key responsibility, to optimize potency and physico-chemical properties of payloads and payloads-linkers.
• The primary responsibilities of suitable candidates will be to impact drug discovery projects by identifying the highest impact computational chemistry approaches for specific projects, and developing and delivering timely, high-quality computational solutions.

You will:

• Participate on multiple interdisciplinary project teams and play a key role in defining project strategies
• Analyze potential payload targets to assess their druggability and determine the most promising approaches.  
• Payloads and linkers suitable for ADCs will be designed in collaboration with the design/synthesis chemists.
• Apply molecular modeling and dynamics, AI and homology modeling and related techniques to understand biological targets and the mechanisms of payloads
• Use both physics-based and AI/ML methods to impact compound design and screening, including design of parallel libraries and singletons.
• Bring new computational approaches from within global Computational Chemistry in Pfizer and the literature to speed ADC discovery.
• Define, implement, and influence project design strategy to deliver projects to key decision points.
• Influence science at both departmental and external level.
• People influence – effective mentor for colleagues in department.

BASIC QUALIFICATIONS:

• The position requires a PhD in computational chemistry or a related discipline and 5+ years of experience in the Biopharmaceutical Industry, applying computer aided drug discovery techniques to various stages of the drug discovery pathway.
• Leading-edge knowledge of computational chemistry principles and a track record of successfully applying them to biopharmaceutical research projects are required.
• The candidate should also have strong Linux and programming skills.
• The candidate should demonstrate the ability to work in a collaborative environment as exemplified by a strong publication record and should have a strong working knowledge of related disciplines in drug discovery such as medicinal chemistry, structural biology, pharmacology and biophysics, in vivo biology, drug metabolism and drug safety.

PREFERRED QUALIFICATIONS:

Preferred candidates will have leading-edge knowledge of the following areas with significant experience with most of them:

• Computational chemistry concepts and techniques (such as structure-based and ligand-based drug design; protein-ligand interactions, docking and scoring; virtual screening; cheminformatics; QSAR and predictive modeling; AI/ML-based protein modeling and homology modeling; molecular dynamics simulations; free energy perturbation methodologies; AI/ML and generative chemistry for drug design; and application of quantum chemical calculations to drug discovery).
• Standard computational chemistry software (such as the Schrodinger suite; CCG MOE; Pipeline Pilot; Gaussian; OpenEye)
• Programming and scripting skills (e.g. Python, Linux workflows); experience deve