Jay Ponder
Washington University in St Louis, MO·Chemistry
DNA and RNA carry the genetic information of life, and they are also drug targets and therapies in their own right. Examples include mRNA vaccines and drugs that act on the nucleic acids of bacteria, viruses and cancer cells.
- Fields
Chemistry
Biophysics
Biochemistry
- Topics
force field
AMOEBA+
molecular dynamics
- Grants
- 1 known grant, through Aug 2027
What they work on
- Develop the AMOEBA+ polarizable multipole force field for DNA and RNA, with parameters generated automatically by the Poltype2 software, to model nucleic acid structure, dynamics and interactions.
- Build AMOEBA+NN by coupling a machine learning potential for local bonding features with classical long-range interactions, aiming for chemical accuracy in nucleic acid binding calculations.
- Implement the new force fields in the GPU-capable Tinker9 molecular dynamics software to enable routine binding free energy estimates for small molecules bound to nucleic acids.
- Apply the models to metal ions binding G-quadruplexes, fluorogenic ligands binding RNA aptamers, antibiotics binding the FMN riboswitch, and the dynamics of the Tetrahymena ribozyme P5abc domain.
More about the research
Computer simulations can show how these molecules move, fold and bind other molecules. However, the simulations are only as good as the force field, the set of equations that describes how atoms push and pull on each other. This project aims to make simulations accurate and efficient enough to routinely calculate how strongly small drug-like molecules bind to DNA and RNA.
Why it matters
Many drugs in development target DNA and RNA, including treatments for bacterial and viral infections, cancers and neurodegenerative diseases. A force field that predicts binding strength to within 1 kcal/mol could let chemists screen and design small molecules and modified oligonucleotides computationally, reducing reliance on trial-and-error experiments. This could help make RNA-targeted drug design faster and more reliable.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Alexander D Mackerell
University of Maryland, Baltimore, MD·Biophysics
Refine the CHARMM36 force field, a model of atomic interactions used in simulations, by directly optimizing Lennard-Jones terms between atom pairs instead of relying on approximate combining rules.
Tai-Sung Lee
Rutgers University-New Brunswick, NJ·Chemistry
Build a Python-based executing environment that connects AMBER's molecular dynamics engine, a free energy module and user workflow control, so new simulation methods can be added and prototyped quickly.
Michael Shirts
University of Colorado Boulder, CO·Chemistry
Build systematically improvable force fields with the Open Force Field Initiative, optimized and validated against new thermophysical data, with statistical tests of when added complexity improves accuracy.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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