Alexander D Mackerell
University of Maryland, Baltimore, MD·Biophysics
Proteins, RNA and sugars are not rigid shapes. They constantly flex and switch between many forms, or conformations, and these shape changes are essential to how they work.
- Fields
Biophysics
Chemistry
Pharmacology
- Topics
molecular dynamics
force field
DGenFF
- Grants
- 1 known grant, through Apr 2029
What they work on
- 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.
- Extend the polarizable Drude force field to carbohydrates, nucleic acids, non-standard amino acids, ions and drug-like molecules, tuning it to reproduce how peptides and short DNA or RNA strands fold and unfold.
- Speed up the sampling of RNA and polysaccharide motions by combining deep neural networks that find key motions with metadynamics and non-equilibrium simulations.
- Scale the SILCS drug-binding mapping method to systems of over a million atoms on GPUs, and use it to estimate pH effects, the role of water, and drug unbinding rates.
- Simulate how magnesium ions shape RNA folding, and how antibody Fc regions interact with Fcγ receptors such as FcγRIIIa to trigger immune signaling inside cells.
More about the research
Ions, nearby molecules and binding partners all affect which shapes appear. Understanding this shape variety helps explain how biomolecules function and helps scientists design drugs. The project builds better computer models of molecules, develops methods to simulate them more efficiently, and applies these tools to RNA, carbohydrates and immune proteins.
Why it matters
More accurate molecular simulations can help researchers predict how candidate drugs bind their targets, which could speed up drug design. The tools are applied to immune responses involving antibodies, with the stated goal of supporting new therapies for infectious diseases and cancer.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jay Ponder
Washington University in St Louis, MO·Chemistry
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.
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.
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.
The school
University of Maryland, Baltimore: 23 labs on PI Pages, $1.5B a year on research, 79 research doctorates a year.
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