Principal Scientist, Structural Biology

F. Hoffmann-La Roche AG; South San Francisco (CA); On-site; USD 151,000 - 280,000; Full time

Benefits offered by this job

Relocation assistance

Discretionary annual bonus

Job summary

Genentech's Department of Protein Sciences in South San Francisco seeks a Principal Scientist in Structural Biology to drive drug discovery by integrating structural data, computational modeling, and biophysical insights.

You will oversee protein construct design, expression, purification, and high‑resolution structure determination using cryoEM and/or X‑ray crystallography, while mentoring cross‑functional teams.

Qualifications

• PhD in Biochemistry, Structural Biology, Biophysics, Computational Biology or related field.
• Minimum 3 years of post‑doctoral experience in industry, academia or a research organization.
• Expert in molecular modeling: MD simulation, ensemble modeling and ensemble docking.
• Biomolecular structure determination via cryoEM or X-ray crystallography.
• Proven use of protein dynamics to enable target discovery and lead optimization.
• Collaborative leader who guides teams based on merit and mutual respect.

Responsibilities

• Lead structural biology strategy and execution within multi-disciplinary teams.
• Oversee protein construct design, expression, purification, and high‑resolution structure determination.
• Solve and analyze structures of target protein complexes with small molecules, peptides or antibodies.
• Utilize computational tools alongside experimental data to characterize dynamics.
• Translate dynamics insights into actionable drug-discovery strategies.
• Mentor colleagues in applying dynamics/ensemble methods and develop workflows.

Skills

Molecular dynamics

Ensemble modeling

CryoEM

X-ray crystallography

Protein dynamics

Protein design

Leadership

Communication

Education

PhD in Biochemistry/Structural Biology/Biophysics/Computational Biology

Tools

Rosetta

Phenix

GROMACS

NAMD

Job description

The Department of Protein Sciences at Genentech seeks an exceptional structural biologist with a focus on protein dynamics to join its Structural Biology group. The ideal candidate will be well-versed in protein production and purification, structure determination of protein and protein-ligand complexes, and an expert in the use of computational and experimental techniques to characterize and understand protein dynamics and ligand binding. Our department offers a highly interdisciplinary environment for drug discovery and biomedical research, with state-of-the-art resources and unparalleled opportunities for scientific collaboration. We integrate macromolecular crystallography, cryoEM, and other methods to drive drug discovery and uncover fundamental biology. Our group designs constructs, purifies proteins, and analyzes their structures and molecular interactions. We collaborate with scientists throughout the Research and Drug Discovery organization to advance discovery of therapeutics.

The Opportunity

As a Principal Scientist in Structural Biology, you will help drive drug discovery initiatives by uncovering the structural and dynamic mechanisms of therapeutic target proteins. Working in a highly interdisciplinary environment, you will integrate structural data, advanced computational modeling, and biophysical insights to enable the discovery of life-changing medicines. Lead structural biology strategy and execution within multi-disciplinary drug discovery project teams, offering actionable structural insights. Oversee protein construct design, expression, purification, and high-resolution structure determination using cryoEM and/or X-ray crystallography. Solve and analyze structures of target protein complexes bound by small molecules, peptides, antibodies or other therapeutic formats. Utilize state-of-the-art computational tools alongside experimental data (cryoEM, HDX) to characterize the dynamics of biological macromolecules. Translate protein dynamics insights into actionable strategies for target assessment, protein construct and reagent design, hit finding, lead identification, lead optimization or other steps of drug discovery. Empower and mentor colleagues in applying computational tools and dynamics/ensemble methods to accelerate drug discovery projects. When appropriate, develop workflows, documentation or training materials.

Who You Are

You are a passionate, collaborative expert motivated by scientific excellence and a desire to deliver innovative solutions for patients worldwide. You thrive in cross-functional environments and lead through scientific influence, open dialogue, and mutual respect. You hold a Ph.D. or equivalent in Biochemistry, Structural Biology, Biophysics, Computational Biology, or a related scientific discipline. You have a minimum of 3 years of relevant post-doctoral experience in industry, academia or a research organization. An expert in molecular modeling techniques such as molecular dynamics simulation, structural ensemble modeling, ensemble docking and/or related techniques. You have demonstrated expertise in biomolecular structure determination via cryoEM or X-ray crystallography. You have a proven track record leveraging insights into protein or protein-ligand molecular dynamics to enable, accelerate, and/or improve target identification, pocket discovery, binder discovery, ligand optimization and/or other steps of drug discovery. A collaborative leader who knows how to guide, inspire and motivate colleagues and teams based on scientific merit and mutual respect, rather than organizational hierarchy. Highly organized, with great attention to detail, strong communication and excellent interpersonal skills.

Preferred:

• You have experience executing or overseeing protein construct design and purification workflows for structural characterization and/or assay development.
• You bring hands-on experience in ligand discovery or lead optimization projects within a multidisciplinary drug discovery environment.
• You possess demonstrated expertise in virtual docking, free energy perturbation (FEP), or related computational chemistry workflows.
• You have a demonstrated interest or experience in protein language models, machine learning for protein design, computational or laboratory automation, or related topics.

Location and Compensation

This is an office- and lab-based position in South San Francisco, CA. This position is eligible for relocation assistance. Please include a cover letter with your application. The expected salary range for this position based on the primary location of San Francisco, CA is $150,700.00 - $279,900.00USD Annual. Actual pay will be determined based on experience, qualifications, geographic location, and other job-related factors permitted by law. A discretionary annual bonus may be available based on individual and Company performance. We are seeking a Principal Scientist to join our team. Depending on the candidate's depth of experience, technical expertise, and leadership background, this role may be leveled at the Senior Principal Scientist level. This position also qualifies for the benefits detailed at the link provided below.

Benefits

Genentech is an equal opportunity employer. It is our policy and practice to employ, promote, and otherwise treat any and all employees and applicants on the basis of merit, qualifications, and competence. The company's policy prohibits unlawful discrimination, including but not limited to, discrimination on the basis of Protected Veteran status, individuals with disabilities status, and consistent with all federal, state, or local laws. If you have a disability and need an accommodation in relation to the online application process, please contact us by completing this form Accommodations for Applicants.

Genentech is an equal opportunity employer. It is our policy and practice to employ, promote, and otherwise treat any and all employees and applicants on the basis of merit, qualifications, and competence. The company's policy prohibits unlawful discrimination, including but not limited to, discrimination on the basis of Protected Veteran status, individuals with disabilities status, and consistent with all federal, state, or local laws. If you have a disability and need an accommodation in relation to the online application process, please contact us by completing this form Accommodations for Applicants.