Principal Scientist/Sr. Principal Scientist, Computational Chemistry & Molecular Design

Antares Therapeutics; Boston (MA); Hybrid; USD 185,000 - 240,000; Full time

Job summary

Antares Therapeutics seeks a Principal or Senior Principal Scientist in Computational Chemistry & Molecular Design to lead the computational chemistry function across discovery programs in Boston. You will apply structure- and ligand-based design, MD, FEP, and machine-learning to drive lead optimization and identify novel targets.

This hands-on role shapes the computational platform, partners with medicinal chemistry, and mentors junior scientists.

Qualifications

• PhD in computational chemistry, biophysics, theoretical chemistry, pharmaceutical sciences, cheminformatics, or related quantitative field.
• PhD with 12+ years (or bachelor’s with 18+ years) for Senior Principal Scientist level, or 10+ years for Principal Scientist.
• Direct contributions to drug discovery programs using computational chemistry and lead optimization.
• Hands-on expertise across structure- and ligand-based design, MD, and free energy methods (FEP).
• Experience applying machine-learning and/or generative design in discovery settings is strongly preferred.
• Experience in covalent drug discovery, covalent docking, warhead selection, and reactivity/selectivity assessment.
• Proficiency with Schrödinger, MOE, OpenEye; programming in Python and data analysis.
• Strong collaboration across disciplines and excellent communication skills.

Responsibilities

• Lead computational chemistry on programs, overseeing target validation, hit identification, and lead optimization.
• Apply structure-based and ligand-based design, MD, and FEP to prioritize compounds and identify binding pockets.
• Integrate machine-learning, generative, and active-learning approaches into design‑make‑test‑analyze cycles.
• Collaborate with medicinal chemistry to translate computational hypotheses into synthesized molecules.
• Lead infrastructure and platform development for computational tools and workflows.
• Analyze data across functions to address critical scientific questions.
• Communicate analyses and recommendations to project teams and leadership.
• Represent computational chemistry in cross‑functional program teams and set design strategy.
• Mentor junior scientists and provide scientific direction as Senior Principal Scientist.

Skills

Structure-based design

Ligand-based design

Molecular dynamics

Free energy methods (FEP)

Machine learning in discovery

Covalent docking

Python programming

Education

PhD in computational chemistry or related field

Tools

Schrödinger suite

MOE

OpenEye

Python scripting

Job description

Principal Scientist/Sr. Principal Scientist, Computational Chemistry & Molecular Design

Salary Band: $185,000-$240,000

Location: Downtown Boston, MA (In-Office 2-3 days/week)

Position Overview

We are seeking an exceptional computational chemist to serve as a scientific leader in molecular design across our discovery portfolio. As a member of a highly integrated team of medicinal chemists, machine learning scientists, structural biologists, biologists, and chemical biologists, you will apply and advance the full range of modern computational methods — structure- and ligand-based design, molecular dynamics, free energy perturbation (FEP), and machine-learning/generative approaches — to assess and prioritize targets, identify high-quality starting points, and drive lead optimization toward development candidates.

This is a hands‑on, high‑impact role on the Antares scientific track. The successful candidate will not only enable programs directly but will also help shape the computational chemistry, machine learning and cheminformatics platform that underpins design across Antares. The role is offered at the Principal or Senior Principal Scientist level; scope, independence, and organizational influence scale with experience, as described under Qualifications.

Key Responsibilities

• Serve as the computational chemistry function lead on programs, providing integrated leadership across target validation, hit identification, hit-to-lead, and lead optimization for multiple small‑molecule programs.
• Apply structure‑based and ligand‑based design, molecular dynamics, and free energy perturbation (FEP) to prioritize compounds, evaluate druggability, and identify and exploit cryptic or novel binding pockets on challenging targets.
• Integrate machine‑learning, generative, and active‑learning approaches into design‑make‑test‑analyze cycles, and multiparameter optimization of potency, selectivity, and ADMET/physicochemical properties.
• Partner closely with medicinal chemistry to translate computational hypotheses into synthesized, tested molecules, and to drive sound decision‑making and smart risk‑taking.
• Lead computational infrastructure and platform development — identifying, evaluating, and deploying best‑in‑class tools, methods, and workflows — and contribute to major collaborations with external partners, in coordination with the Discovery Predictive Sciences team.
• Analyze and integrate data across functions to independently identify, define, and address critical scientific issues and key scientific questions.
• Communicate analyses, models, and recommendations clearly to project teams and leadership, influencing program strategy and portfolio decisions.
• Represent computational chemistry in cross‑functional program teams; help set design strategy and define the questions that computation should answer at each stage.
• Mentor junior scientists and, at the Senior Principal level, provide broad scientific direction, establish best practices, and act as a recognized technical authority internally and in the external scientific community.

Qualifications

• PhD. in computational chemistry, biophysics, theoretical chemistry, pharmaceutical sciences, cheminformatics, or a related quantitative field (or equivalent experience).
• Principal Scientist: PhD with 10+ years (or bachelor’s with 16+ years) of computational chemistry experience in a pharmaceutical and/or biotechnology setting. Senior Principal Scientist: PhD with 12+ years (or bachelor’s with 18+ years), with a demonstrated track record of independent scientific leadership, cross‑functional influence, and organizational impact.
• Demonstrated, direct contributions to drug discovery programs through the application of computational chemistry — ideally including progression of compounds into or toward the clinic.
• Deep, hands‑on expertise across modern computational methods: structure‑ and ligand‑based design, molecular dynamics, and free energy methods (e.g., FEP).
• Experience applying machine‑learning and/or generative molecular design methods in a discovery setting is strongly preferred.
• Experience in covalent drug discovery — including covalent docking, warhead selection and reactivity/selectivity assessment, and modeling of covalent kinetics (e.g., kinact/Ki) — is strongly preferred and is central to Antares' programs.
• Proficiency with the Schrödinger suite and/or comparable platforms (e.g., MOE, OpenEye), and programming/scripting in Python and with coding assistants like Claude Code/Codex for cheminformatics and data analysis.
• Strong understanding of medicinal chemistry, structural biology, and DMPK principles, and a proven ability to collaborate effectively in a fast‑paced, matrixed, team‑based environment.
• Excellent written and verbal communication skills, with the ability to convey complex computational concepts to multidisciplinary audiences.
• A passionate, results‑oriented drug hunter who thrives in a collaborative, data‑driven, and scientifically ambitious culture.

The anticipated annual salary range for this position is $185,000-$240,000 annually. The actual salary offered will be based on a number of factors, including but not limited to the qualifications of the applicant, years of relevant experience, level of education attained, certifications or other professional licenses held, and if applicable, the location in which the applicant lives and/or from which they will be performing the job.