Associate Director/Director, Computational Chemistry

Flagship Pioneering•Cambridge, MA

4d•$176,000 - $253,000

About The Position

Flagship Labs 111 Inc. (FL111) is a privately held, early-stage biotechnology company pioneering a novel platform harnessing innovations in chemistry, computation, and data science to create new therapeutic modalities beyond traditional small molecules. FL111 is backed by Flagship Pioneering, bringing the courage, vision, and resources to guide FL111 from platform validation to patient impact. We are seeking collaborative, creative and relentless problem solvers that share our passion for impact to join us! THE ROLE FL111 is seeking an AD/D, Computational Chemistry to play a central role in the design and optimization of heterobifunctional small molecules. This individual will work closely with medicinal chemists, biologists, and in vivo pharmacologists to develop and apply computational tools to guide molecular design decisions across the design–build–test–learn cycle. The successful candidate will contribute directly to molecular ideation, property optimization, and compound prioritization, with a particular focus on the unique challenges of heterobifunctional molecules. This is a hands-on, high-impact role in a fast-paced startup environment where computational insights directly shape experimental strategy.

Requirements

PhD in Chemistry, Medicinal Chemistry, Computational Chemistry, or a related discipline, with 5+ years of relevant industry experience (or equivalent experience).
Hands-on experience in computational medicinal chemistry or structure-based drug design.
Demonstrated ability to propose and evaluate real, synthetically actionable molecular designs.
Experience using cheminformatics tools for compound design, analysis and prioritization.
Strong collaboration and communication skills: ability to work effectively in interdisciplinary teams.

Nice To Haves

Prior experience working on heterobifunctional small molecules (e.g., PROTACs) is preferred
Familiarity with ADME optimization challenges for large, flexible molecules is strongly preferred.
Prior experience in an early-stage or startup biotech environment is preferred.

Responsibilities

Molecular Design & Optimization: Propose & evaluate heterobifunctional small molecule designs, including ligand selection, attachment vectors, and linker architectures, with a strong focus on balancing target engagement, molecular properties, and synthetic efficiency.
Cheminformatics & Library Exploration: Perform cheminformatics analyses to identify chemical series that enable improved property profiles and simplified syntheses
ADME & Developability Assessment: Evaluate and predict key molecular properties (e.g., solubility, permeability, lipophilicity, clearance risk) and help prioritize compounds by integrating developability considerations.
Structure-Based & Computational Modeling: Apply structure-based modeling tools (e.g., docking, conformational analysis) to inform ligand selection, attachment strategy, and linker design, translating computational insights into clear, actionable design recommendations.
Cross-Functional Collaboration: Work closely with chemistry, biology, and in vivo pharmacology teams to guide experimental planning, inform design–make–test cycles, and communicate computational insights clearly in project discussions and presentations.