Head of Molecular Dynamics for RNA Therapeutics

Lilly; South San Francisco (CA); Vor Ort; USD 168.000 - 264.000; Vollzeit

Benefits dieser Stelle

Annual bonus

Comprehensive benefits

Zusammenfassung

Lilly’s RNA Therapeutics is seeking a computational biophysicist in South San Francisco to build atomic-resolution models of how chemical modifications influence Ago2 loading and catalytic activity. You’ll develop MD and free-energy models from cryo-EM and biophysical data to guide medicinal chemistry decisions across siRNA programs.

You will lead hands-on simulations as an individual contributor and, in the near term, help lead a team of senior computational scientists while collaborating with

Qualifikationen

• PhD in biophysics, computational chemistry, chemical physics, structural biology or a related STEM field.
• Five+ years of relevant experience (postdoctoral or industry) running and analyzing molecular dynamics simulations of protein–nucleic acid systems.
• Experience with MD engines (AMBER, GROMACS, NAMD, OpenMM, CHARMM or equivalent) and free-energy methods (FEP, TI, umbrella sampling, metadynamics).

Aufgaben

• Model how chemical modifications affect duplex thermodynamics, Ago2 binding and RISC catalytic efficiency.
• Run all-atom, enhanced-sampling and coarse-grained simulations of siRNA duplexes and Ago2 complexes.
• Quantify energetics and dynamics of loading, seed-pairing nucleation, passenger-strand ejection and cleavage.
• Model seed-mediated off-target engagement and balance potency vs off-target activity.
• Convert simulation output into design hypotheses and work with medicinal chemists to prioritize modifications.
• Test predictions against biophysical and functional data and revise models accordingly.
• Build and maintain simulation pipelines and force-field parameters for non-natural nucleotides.
• Present findings and recommendations to chemists, biologists and leadership; publish and patent as appropriate.

Kenntnisse

Molecular dynamics simulations

Biophysics

Python

Computational chemistry

Ausbildung

PhD in biophysics / computational chemistry

Tools

AMBER

GROMACS

NAMD

OpenMM

CHARMM

FEP/TI

Umbrella sampling

Metadynamics

Jobbeschreibung

Lilly’s RNA Therapeutics is seeking a computational biophysicist in South San Francisco to build atomic-resolution models of how chemical modifications influence Ago2 loading and catalytic activity. You’ll develop MD and free-energy models from cryo-EM and biophysical data to guide medicinal chemistry decisions across siRNA programs.

You will lead hands-on simulations as an individual contributor and, in the near term, help lead a team of senior computational scientists while collaborating with