Senior Principal Research Scientist, Physics-Based Methods Development

Job Description

We are seeking a highly motivated and experienced Computational Chemist to join our Data and Computational Sciences Group in Boston to lead scientific innovation in physics-based molecular modeling and simulations. As a recognized expert and thought leader, you will develop the company’s physics-based computational methods platform: prototype, benchmark, and implement computational methodologies, collaborate with software engineers to scale solutions across with organization, collaborate with other scientists to establish best practices, and drive global alignment to accelerate drug discovery. This is a highly visible, scientifically influential role with broad impact across multiple therapeutic areas.

This is a Boston based, hybrid position requiring 3 days/week onsite.

Key Responsibilities:

• Develop, implement, and optimize advanced physics-based methods including:
  • Alchemical and endpoint free energy methods (e.g., FEP, MM/GBSA) for potency, selectivity, and optimization.
  • High-performance molecular dynamics (MD) and enhanced sampling (e.g., metadynamics, REST) to explore conformational landscapes and transitions.
  • Refinement of artificial intelligence derived protein structures to resolve ambiguous or flexible regions and preparation of active site-ready structures for reliable docking.
  • Virtual screening workflows using physics-based docking and scoring.
  • Model complex drug modalities beyond Ro5 such as peptides with conformational constraints and challenging permeability profiles.

• Collaborate with ML/AI scientists and computational chemists to evaluate and implement ML enabled physics-based methods
• Serve as a technical and scientific SME, influencing both strategic direction and day-to-day execution.
• Work with scientific engineers to ensure high-performance physics-based platforms are robust and accessible from cloud and on-prem compute resources.
• Proactively seek opportunities to enhance Vertex’s global R&D efforts through cross-functional collaboration with Structural Biology, and Data Science teams
• Stay at the forefront of computational chemistry innovations, proactively incorporating emerging tools and technologies to enhance team capabilities
• Mentor and guide junior scientists, fostering a culture of innovation, collaboration and scientific excellence

Skills and qualifications required:

• Ph.D. in Computational Chemistry, Biophysics, Chemical Physics, or related field with 6+ years of post-Ph.D. experience in biotech, pharma, or academic research or Master's and 9+ years, or Bachelor's and 11+ years
• Expertise in free energy methods, molecular simulations, and computational drug design.
• Demonstrated experience in developing methods with successful impact in translating to real-world drug discovery. Deep understanding of protein-ligand interactions, and membrane systems.
• Fluency with simulation packages (e.g., AMBER, GROMACS,,) and familiarity with common toolkits such as OpenMM, OpenFF
• Strong software development skills in Python, and C/C++ and scripting (Python, Bash, etc.) and familiarity with modern software development practices
• Excellent leadership, communication and decision-making skills, fostering collaboration across teams

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Pay Range:

$162,400 - $243,600

Disclosure Statement:

The range provided is based on what we believe is a reasonable estimate for the base salary pay range for this job at the time of posting. This role is eligible for an annual bonus and annual equity awards. Some roles may also be eligible for overtime pay, in accordance with federal and state requirements. Actual base salary pay will be based on a number of factors, including skills, competencies, experience, and other job-related factors permitted by law.

At Vertex, our Total Rewards offerings also include inclusive market-leading benefits to meet our employees wherever they are in their career, financial, family and wellbeing journey while providing flexibility and resources to support their growth and aspirations.  From medical, dental and vision benefits to generous paid time off (including a week-long company shutdown in the Summer and the Winter), educational assistance programs including student loan repayment, a generous commuting subsidy, matching charitable donations, 401(k) and so much more.

Flex Designation:

Hybrid-Eligible Or On-Site Eligible

Flex Eligibility Status:

In this Hybrid-Eligible role, you can choose to be designated as: 
1.    Hybrid: work remotely up to two days per week; or select
2.    On-Site: work five days per week on-site with ad hoc flexibili