Consultant, Computational Chemistry

2 weeks ago

San Francisco, California, United States Generalproximity Full time
tl;dr

General Proximity is a seed-stage startup developing the next generation of induced-proximity medicines. 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 first-rate Computational Chemists, with previous experience developing PROTACs or related induced-proximity drugs, 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], 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, 3, 4], and our technology holds the same promise.

The Position

We are seeking an experienced Computational Chemist to be a founding member of our Drug Discovery Team. In this position you will work in close conjunction with our Medicinal Chemistry Team in the design and optimization of a completely novel class of therapeutics.

Your responsibilities will include: Spearheading the modeling and informatics initiatives on team projects, strategically applying computational methodologies throughout all stages of the drug discovery process, predicting binding modes and ternary complexes, analyzing crystal structure data, designing and optimizing first-in-class bifunctional molecules, collaborating with our Drug Discovery and IP team on patent applications, and spearheading forays into new disease areas.

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 Biology, Pharmacology, or related field
  • 5-10+ years of industry experience (job title commensurate with experience)
  • Deep understanding of small-molecule drug discovery and its relationship to human disease:
    • Expertise in creating homology models, prediction of protein-protein interaction interfaces, and docking of small molecules including molecular glues or bifunctional molecules (e.g. PROTACs or other CIDs)
    • Experience with lead identification and lead optimization of diverse therapeutic modalities
  • Programming/scripting proficiency in Python, including experience manipulating large datasets
  • Evidence of creative application of computational chemistry approaches to problems of biological interest, demonstrated through multiple publications and external presentations
  • Experience with structural biology laboratory techniques (protein production, purification, and crystallography)
  • Experience predicting binding modes of ternary complexes
Nice to have:
  • Molecular dynamics drug discovery experience
  • Familiarity with Linux and high-performance computing
  • Experience applying computational methods such as molecular dynamics, quantum chemistry, and deep learning to problems of biological interest
  • Ability to use molecular modelling packages such as MOE, Schrodinger, PyMOL and OpenEye
  • Have experience with Cheminformatics tools such as Datawarrior, Spotfire to analyze and visualize the data
  • Experience with structural biology laboratory techniques (protein production, purification, and crystallography)
  • Excited to learn and implement novel technologies including Al/ML to advance the pipeline
  • Experience working in multidisciplinary teams that include experimental scientists
  • Prior experience on teams that have successfully advanced research to the clinic
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


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