Computational Chemistry Scientist – Center for Protein Degradation

Dana Farber Cancer Institute

Boston, MA

The Center for Protein Degradation (CPD) seeks a highly motivated individual to join the multidisciplinary team as a computational chemist to develop and apply cutting-edge computational techniques to guide the design and optimization of small molecule protein degraders as well as the identification of protein interfaces for ligand induced dimerization. The candidate will closely work with chemists, structural biologists and proteomics experts to advance the medicinal chemistry of protein degraders by providing in silico prediction of molecular properties and mechanistic insights at atomic level.

This individual will be an important member of our research team and will be centrally involved in assisting various research projects primarily involving protein biochemistry. In addition to the bench-based research, responsibilities will also include some aspects of laboratory management and organization. Training is available in all aspects of experimental research.

Dana-Farber Cancer Institute (DFCI) and Deerfield Management have entered a multi-year collaboration to create the Center for Protein Degradation (CPD) at DFCI led by Drs. Fischer and Gray.  The goals of the Center for Protein Degradation are to create a next-generation protein degrader platform and interrogate and advance a large portfolio of protein degrader targets.  This is an exceptional opportunity to join a newly founded research center that is pushing the boundaries of targeted protein degradation research and accelerating the translation of basic science into clinical solutions.

Significant progress has recently been made towards chemically induced targeted protein degradation using heterobifunctional small molecule ligands (often referred to as degraders or PROTACs). Small molecule degraders commonly comprise an E3 ligase binder linked to a target binder through a chemical linker. While many targets are amenable for proteolytic degradation, the design of the degraders is empirical. We have recently shown that plasticity of target protein binding can be recapitulated computationally and thus enable rational design of degraders (Nature Chemical Biology, https://www.nature.com/articles/s41589-018-0055-y).

Responsibilities:

• Work closely with medicinal chemists to guide the optimization of lead compounds
• Independently plan, manage, and perform research and projects. Develop project proposals, timelines and resource needs.  Monitor milestones and ensure deliverables are completed on time.
• Take an independent and active role in development of novel computational methods for design of protein degraders
• Support the needs of multiple small molecule drug discovery projects.
• Collect and analyze data, generate hypothesis, and identify next steps based on outcomes
• Take an active role in developing computational design platform for protein degraders
• Communicate project deliverables to the leaders across the group, and other senior governance groups when necessary
• Interact and liaise with internal experts, external experts, academic groups, and CROs to establish and direct collaborations and projects
• Prepare papers and publications, if necessary
• Maintain clear and accurate records of research work (e.g., research methods, results/findings)
• Maintain, comment, and deposit all code to GitHub.

Qualifications:

• Ph.D. in computational chemistry, computational biophysics, or related fields.
• Strong working experience in structural and ligand based small molecule drug design.
• Good programming/scripting skills are essential for this position.
• Excellent communication and presentation skills.
• Scientific drive, demonstrated by a proven track record of publications in peer reviewed journals
• Demonstrated ability to work in a fast-paced and dynamic environment.
• Ability to work independently as well as in a collaborative and team environment
• Excellent organizational and prioritization skills. Strong attention to detail
• Ability to collect and analyze experimental data, prepare research publications and communicate results.
• Programming/scripting skills are essential for this position.
• Experience in molecular dynamics simulation, protein docking, and cheminformatics is desired.

About Dana Farber:

Located in Boston and the surrounding communities, Dana-Farber Cancer Institute brings together world renowned clinicians, innovative researchers and dedicated professionals, allies in the common mission of conquering cancer, HIV/AIDS and related diseases. Combining extremely talented people with the best technologies in a genuinely positive environment, we provide compassionate and comprehensive care to patients of all ages; we conduct research that advances treatment; we educate tomorrow's physician/researchers; we reach out to underserved members of our community; and we work with amazing partners, including other Harvard Medical School-affiliated hospitals.

To apply, please visit: https://careers-dfci.icims.com/jobs/17275/computational-chemistry-scientist-%e2%80%93-center-for-protein-degradation/job?iis=Social+Networks&iisn=Paula+Conley&iieid=pe1572887880618862f9&iispid=88818

Dana-Farber Cancer Institute is an equal opportunity employer and affirms the right of every qualified applicant to receive consideration for employment without regard to race, color, religion, sex, gender identity or expression, national origin, sexual orientation, genetic information, disability, age, ancestry, military service, protected veteran status, or other groups as protected by law.