Ao Ma
University of Illinois Chicago, IL·Biophysics
Most drugs work by binding to a protein, but proteins are not rigid locks. They flex and change shape as a drug or other small molecule (a ligand) moves in, and surrounding water molecules also shape the process.
- Fields
Biophysics
Chemistry
Pharmacology
- Topics
protein-ligand binding
protein conformational dynamics
molecular dynamics
- Grants
- 2 known grants, through Aug 2028
What they work on
- Compute true reaction coordinates for ligand binding using energy flow theory and the generalized work functional method, then simulate natural, unbiased binding in HIV-1 protease and PDZ domains.
- Determine how protein shape changes and water dynamics together control binding free energies and rate constants in conformational selection (HIV-1 protease) versus induced fit (PDZ domains).
- Develop a method to split ligand binding free energy into contributions from individual residue-residue interactions, and use it to find interactions behind resistance to HIV-1 protease inhibitors.
- Design HIV-1 protease mutations predicted to strengthen or neutralize drug resistance, and test these computational predictions in virus infection assays.
More about the research
Knowing exactly which motions control binding could explain why some drugs stick tightly and why viruses evolve resistance. The lab uses physics-based computer simulation to uncover these motions. One project studies the basic mechanism of binding. The other applies it to drug resistance in HIV.
Why it matters
HIV drug resistance threatens lifelong treatment for people living with HIV/AIDS. A rigorous toolkit that explains resistance could help design next-generation antivirals that work against current resistant strains and make new resistance less likely. More broadly, understanding how protein motions and water control binding could inform drug discovery and protein engineering.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jonah Vilseck
Indiana University-Purdue University-Indianapolis, IN·Chemistry
Use lambda dynamics free energy simulations to understand how missense mutations in a drug target cause drug resistance, and to identify drug modifications that overcome it.
Ronald Levy
Temple University, PA·Biophysics
Determine the physical basis of epistasis, where one mutation's effect depends on others, in HIV integrase and capsid under different drugs, using molecular dynamics simulations and virus data to build drug-specific fitness landscapes.
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.
The school
University of Illinois Chicago: 42 labs on PI Pages, $532M a year on research, 359 research doctorates a year.
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