General Proximity · San Francisco, CA
Scientist/Sr. Scientist, Computational Chemistry
TL;DR General Proximity is a seed-stage startup developing the next generation of induced proximity medicines (IPMs). Our OmniTAC drug discovery engine furnish...
TL;DR
General Proximity is a seed-stage startup developing the next generation of induced proximity medicines (IPMs). Our OmniTAC drug
discovery engine furnishes molecules that co-opt existing cellular machinery to overcome therapeutic challenges, which have
remained unapproachable to other modalities for decades.
We are seeking a first-rate [https://www.youtube.com/watch?v=Uyzqmn8Azuo] computational chemist to help us pioneer this uncharted
frontier of drug discovery.
---------------------------------------------------------------------------------------------------------------------------------
OUR STORY
A long-standing challenge in drug discovery is the development of molecules capable of modulating difficult or "undruggable"
targets. Disease-causing proteins can be dysfunctional in many different ways, but our armamentarium for fixing them is quite
limited. The most common mechanism of action for FDA-approved drugs is inhibition[1]
[https://www.nature.com/articles/nrd.2016.230], but there are many other possible perturbation types whose potential remains
unrealized.
General Proximity is a seed-stage drug discovery company developing a novel platform technology to solve this problem. We make
bifunctional drugs that induce the modification of drug targets by existing cellular machinery (rather than through direct
modulation by the drug, the classical approach).
Historically, the development of technologies that allow one to push new buttons in biology has been an incredibly fertile field
for the discovery of new medicines[2 [https://www.nature.com/articles/nrd3410], 3 [https://www.nature.com/articles/nrd.2016.213],
4 [https://www.nature.com/articles/nrd.2016.211]], and our technology holds the same promise.
THE POSITION
We are seeking an exceptional computational chemist to support our computational chemistry, cheminformatics, and molecular design
efforts. This role will help drive small-molecule drug discovery programs by providing practical modeling support, applying modern
computational workflows, and using the cheminformatics and AI-enabled tools that empower medicinal chemists and project teams.
The successful candidate will be a hands-on drug designer: someone who can partner closely with medicinal chemists, structural
biologists, biologists, and DMPK scientists to guide compound design from hit identification through lead optimization and
candidate selection. They will also apply practical tools that improve decision-making, accelerate
design-make-test-analyze cycles, and make computational and AI-driven methods accessible to bench chemists.
The ideal candidate is a computational drug hunter who combines strong technical expertise with practical medicinal chemistry
judgment. This person should not be an isolated modeler, but a true project partner who sits with chemistry teams, understands the
design problem, proposes molecules, helps interpret data, and contributes tools that make the broader organization faster and
smarter.
This role is ideal for someone who has worked in a pharma or biotech computational chemistry group and wants to work with modern,
AI-enabled computational methods while remaining directly involved in molecule design.
WHAT YOU'LL DO
Computational Chemistry and Molecular Design
Provide hands-on computational chemistry support to small-molecule discovery programs from target evaluation, hit identification,
hit-to-lead, and lead optimization through candidate nomination.
Apply structure-based and ligand-based design approaches to guide compound design, including docking, molecular dynamics,
pharmacophore modeling, QSAR, scaffold hopping, virtual screening, FEP/free-energy methods, and multi-parameter optimization.
Use structural biology data, including X-ray structures, cryo-EM structures, homology models, and AlphaFold-derived models, to
generate actionable design hypotheses.
Partner with the medicinal chemistry team to interpret SAR, optimize potency, selectivity, physicochemical properties, ADME/PK,
developability, and synthetic feasibility.
Contribute to computational design discussions with project teams and translate complex modeling results into clear, practical
medicinal chemistry recommendations.
Support portfolio prioritization by evaluating target tractability, ligandability, binding-site quality, chemical matter, and
developability risks.
Cheminformatics and Data Infrastructure
Use and help improve chem and bioinformatics tools that support compound registration, structure-searching, SAR analysis, property
visualization, compound triage, library design, and project decision-making.
Apply tools for chemical data handling, including similarity and substructure searching, R-group analysis, matched molecular
pairs, reaction enumeration, compound clustering, property prediction, and visualization.
Work with internal or external engineering and data science teams to integrate chemical, biological, DMPK, structural, and assay
data into usable project dashboards and design tools.
Follow best practices for chemical data quality, assay data curation, compound annotation, metadata standards, and reproducible
computational workflows.
Use commercial and open-source computational tools, including platforms such as Schrödinger, MOE, CCDC tools, ChemAxon, KNIME,
Pipeline Pilot, RDKit, DataWarrior, Spotfire, and related systems.
AI/ML and Digital Chemistry Tools
Apply user-friendly AI/ML-enabled molecular design tools, including generative chemistry, predictive ADME/Tox models, property
prediction, active learning, virtual screening, and decision-support systems.
Help incorporate AI tools into the DMTA cycle, including compound prioritization, library design, synthetic route ideation,
molecular-property prediction, and design hypothesis generation.
Support AI literacy across chemistry and project teams by helping colleagues understand appropriate use, limitations, and
interpretation of predictive models.
Help develop workflows that allow medicinal chemists to use modeling and AI tools without requiring deep computational expertise.
Collaboration and Continuous Improvement
Contribute to the computational chemistry approach for projects and align it with discovery program needs.
Serve as a subject-matter resource for computational chemistry, cheminformatics, AI-enabled design, and molecular modeling.
Support collaborations with CROs, software vendors, academic groups, and computational chemistry consultants where appropriate.
Represent computational chemistry in project team meetings and program discussions.
Maintain awareness of emerging computational, AI, and cheminformatics technologies and recommend adoption where scientifically and
operationally justified.
ABOUT YOU
High Agency. Initiative, independence, and self-accountability are some of our most valued traits.
Enthusiastic. We love people who are excited about what they are doing and are generally attempting to build a high-energy team.
Intensity and Grit. Early-stage startups are hard. Drug discovery is doubly so. We are looking for candidates who have a
demonstrated ability to stick with complex problems for the long haul, with a team that has your back along the way.
Prosocial. We are here to create life-saving medicines for the patients who need it most. You should be, too.
QUALIFICATIONS & NICE-TO-HAVES
- PhD in Computational Chemistry, Medicinal Chemistry, Chemical Physics, Biophysics, Cheminformatics, Physical Organic Chemistry,
or a related discipline.
- A minimum of 3 years of relevant experience in pharma, biotech, or a drug discovery-focused research environment.
- Track record of using computational chemistry to impact small-molecule drug discovery programs, ideally through hit-to-lead or
lead optimization.
- Hands-on expertise in structure-based drug design, ligand-based design, docking, molecular dynamics, virtual screening, QSAR,
FEP/free-energy methods, pharmacophore modeling, and multi-parameter optimization.
- Strong working knowledge of medicinal chemistry principles, SAR interpretation, physicochemical property optimization, ADME/PK
concepts, and developability considerations.
- Practical experience with cheminformatics platforms, chemical databases, chemical data curation, compound registration systems,
and project-facing visualization tools.
- Experience with AI/ML applications in molecular design, including predictive modeling, generative chemistry, active learning,
or AI-enabled compound prioritization.
- Strong programming or scripting ability, preferably Python, with experience using cheminformatics toolkits such as RDKit and
modern data science workflows.
- Ability to communicate complex computational concepts clearly to medicinal chemists, biologists, and non-specialist
stakeholders.
- Ability to collaborate within cross-functional teams and influence project decisions through strong scientific input.
- Nice to have:
- Experience working in a biotech or fast-moving discovery organization
- Experience implementing user-friendly modeling tools for medicinal chemists
- Familiarity with cloud-based or high-performance computing environments
- Experience with automated DMTA workflows, electronic lab notebooks, compound management systems, assay-data systems, and
integrated discovery platforms
- Experience supporting discovery across multiple modalities, such as covalent inhibitors, bifunctional molecules, and
molecular glues
- Familiarity with synthetic accessibility prediction, retrosynthesis tools, reaction enumeration, and library design
- Scientific contributions through publications, presentations, patents, open-source contributions, or demonstrated project
impact
BENEFITS [https://www.generalproximity.bio/benefits]
- Strong equity incentives. We are looking for candidates who will bring a strong sense of ownership to drive their project areas
forward, and we believe that you deserve to be compensated accordingly.
- Top tier medical, dental, and vision coverage + One Medical membership.
- 401(k) retirement plans.
- Education and health/fitness incentive programs.
- Meditation retreats—do a ten-day Vipassana retreat without counting towards vacation days.
- Reading budget! We will buy you books. 📚
- Located in the MBC BioLabs at 135 Mississippi Street, an entrepreneurial hub full of the best scientists and operators the Bay
Area has to offer. Our lab is a very short walk from the 22nd St Caltrain Station and a number of wonderful restaurants and
cafés.
ABOUT US
Work Hard/Play Hard. We believe time is our most valuable commodity, so we strive to create a culture that reflects this. We won’t
drag you through unnecessary meetings or email you at 7 PM on a Saturday. When we're at work, we're there to get things done, and
when we're off, we're really off. 🌴
Strong Communication. We like well-written documents over PowerPoints, OKRs over vague mission statements, and weekly one-on-ones
over yearly reviews.
Writing First. We have a "writing-first" culture. We believe that clarity of writing reflects clarity of thinking and that the
benefits of well-written documentation in a scientific environment are innumerable: democratization of ideation and
decision-making, increased reproducibility, quicker scaling and onboarding, and better company-wide alignment, to name a few.
Growth. As an early-stage startup, we value scientists with an independent, can-do attitude. The more hats you can wear, the
better. Our job as employers is to put you in positive feedback loops so you can grow in the direction of your choosing.
---------------------------------------------------------------------------------------------------------------------------------
Title and compensation commensurate with experience. Applications from candidates of diverse backgrounds, women, and members of
underrepresented minority groups are particularly welcomed. We look forward to hearing from you. :)
More info at jobs.generalproximity.bio [https://jobs.generalproximity.bio/]
Roll
Scientist/Sr. Scientist, Computational Chemistry
Kategori
Other
Plats
Publicerad
29 juli
Sista ansökningsdag
29 augusti
Källa