Ronald Levy
Temple University, PA·Biophysics
Proteins change shape, bind drugs and pick up mutations, and each of these depends on the physics of their atoms and on how mutations at different positions interact. The lab combines two computational views of proteins.
- Fields
Biophysics
Chemistry
Microbiology & Immunology
- Topics
drug resistance
antiretroviral therapy
HIV integrase
- Grants
- 2 known grants, through Jul 2028
What they work on
- 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.
- Use large-scale alchemical free energy simulations, which computationally swap one amino acid for another, to measure how mutations destabilize the protein contacts that hold the HIV intasome and capsid together.
- Determine why HIV integrase inhibitors bind in multiple ways and how surrounding water helps them bind strongly, and develop tools for refining these binding modes in cryo-EM structures.
- Combine sequence co-variation machine learning and molecular dynamics to map how protein kinases switch between active and inactive states, including the P-loop and substrate binding by Src tyrosine kinases.
- Detect multi-residue allosteric pathways, groups of residues that pass signals through a protein, in kinases and extend the methods to GPCRs and the HIV intasome.
- Calculate the thermodynamics of water molecules at protein surfaces to refine solvent in cryo-EM maps, and predict how displacing water in binding sites affects drug binding.
More about the research
Molecular dynamics simulations track the motions of every atom. Physics-based machine learning models learn from many related protein sequences which positions tend to mutate together (sequence co-variation). Both projects use this pairing, together with experimental collaborators, to explain protein function, drug resistance, and drug binding.
Why it matters
Antiretroviral therapy for HIV eventually fails as the virus becomes drug resistant. Tools that forecast how HIV mutates under drug pressure could help individualize treatment and design new drug combinations for people living with HIV. Mapping kinase shapes and binding sites could guide more specific anti-cancer drugs. Better placement of water in cryo-EM structures may help researchers design drugs that bind more tightly.
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.
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.
Brian Kuhlman
University of North Carolina at Chapel Hill, NC·Biochemistry
Test whether a protein core mixing water-repelling and water-attracting amino acids yields a partly unfolded, water-containing cold state, using de novo designed cold unfolding proteins, biophysical measurements and molecular dynamics simulations.
The school
Temple University: 22 labs on PI Pages, $315M a year on research, 238 research doctorates a year.
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