• Full Time
  • Boston, MA

Company 

Silicon Therapeutics (“SITX”) is a privately-held, physics-driven integrated drug discovery company in the preclinical IND stage targeting innate immunity to start, but with the capability to move into many other franchise opportunities. The Company’s initial pipeline is focused on modulation of the innate immune system to “light the spark” within immunologically cold tumors by using its physics-enabled drug discovery engine for the design of small molecule therapeutics and the lead program is in late stage preclinical studies. SITX’s discovery efforts as well as physics-based platform are all completely in-house, with a full wet lab as well as a team of over 25 experienced R&D professionals spanning biology, biochemistry, chemistry, biophysics (NMR + X-ray) & preclinical sciences. SITX’s engine leverages quantum mechanics and molecular dynamics, which are deployed on its own internal super computer composed of over 400 GPU’s and FPGA’s and allows SITX to accurately simulate the physical motion and properties of biological targets at an atomistic level resolution. The platform is completely proprietary to SITX and was built from the ground up with the purpose of addressing difficult targets and using simulations to break through bottlenecks that has plagued traditional drug discovery approaches on such targets. It is currently the ONLY company which owns the entire spectrum of physics-driven drug discovery from chip-to-clinic with a team of over 40 individuals in Boston.

The Company’s initial focus in on innate immunity and its pipeline is currently composed of one project entering into IND-enabling studies, another one entering hit-to-lead and two more ramping up. It’s unique advantage in designing small molecules using all atom simulations has allowed it to advance a systemically available small molecule STING agonist into a preclinical development. The program is ramping up for IND enabling studies entry to the clinic in 2020. This differentiated product can be administered systemically via an IV dose and has single agent effects in early mouse efficacy studies using PD1 resistant tumor models and is a “rule-of-5” compliant small molecule. Beyond this one program, the Company is also advancing an ADAR inhibitor which can be considered an innate immune check-point as well as a multitude of targets that explore Innate Immunity’s role in cancer biology.

SITX was founded out of the BIDMC in late 2016 and has raised ~50mm USD to date from leading investors including Sequoia & Chengwei Capital. The Company’s investors are long-term, premier brands that have the capability to hold businesses for decades and are believers in SITX’s mission and physics-driven approach.

Job Summary

Silicon Therapeutics seeks an outstanding computational chemist with experience in applying state-of-the-art computational methods to drive the design of small-molecule drugs against biological macromolecules associated with disease.

Job Responsibilities

  • Work with medicinal chemists and computational scientists to interpret structural information and computer simulation data, to optimize small molecule drug candidates.
  • Participate on our exploratory project teams to computationally evaluate the druggability of new protein targets and help drive the early stage SiTX discovery portfolio.
  • Apply state-of-the-art computational methods to interrogate protein dynamics, structure, and function to support internal drug discovery projects.
  • Routinely engage internal simulation experts and scientific programmers to develop and improve proprietary computational applications that are aligned with project deliverables.
  • Communicate simulation data and molecular design rationales to cross-functional teams to help drive project priorities and decision making.
  • Maintain a working knowledge of contemporary computational chemistry methods and their use in molecular design and data analysis as applied to drug design projects.

Required Skills & Qualifications

  • PhD with 2+ years of postdoctoral and/or industry experience in computational chemistry, structure-based and computer-aided drug design, medicinal chemistry, structural biology or related field.
  • Hands-on experience and deep understanding of state-of-the-art computational techniques, including docking, protein dynamics, homology modeling, and free energy methods (both alchemical and path-based).
  • Fundamental knowledge of structure-based drug design (SBDD), ligand conformation, protein structure and function, and protein- ligand interactions.
  • Comfortable with command-line based computational environment and proficient with scientific programming using Python.
  • Deep expertise and sold track record of productivity as evidenced by publications in high-impact peer-reviewed journals and/or patents.
  • Desire to work on a multidisciplinary team with chemists, biologists, and biophysicists on drug discovery projects.
  • Excellent communication and collaboration skills with ability to work in a multidisciplinary environment.
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