Patel Dry LabUniversity of Idaho

Research

We study how sequence and structure determine protein function, evolution, and response to therapeutics, combining molecular simulation with machine learning.

Vision & opsins

Small changes in an opsin's amino-acid sequence shift the wavelength of light it absorbs. We combine atomistic molecular dynamics with machine learning to predict spectral sensitivity in vertebrate visual pigments and microbial rhodopsins, and work with experimental collaborators on the evolution and development of vision in fishes.

Rhodopsin (wild type) in a lipid membrane, from our 1 µs molecular dynamics simulation. Retinal in gold.
Rhodopsin (wild type) in a lipid membrane, from our 1 µs molecular dynamics simulation. Retinal in gold.

Viruses & antibody escape

We use structural modeling and MD+FoldX to predict how mutations change binding between viral proteins and antibodies or host factors, with applications to SARS-CoV-2, Ebola virus, RSV, HIV, H5N1 influenza, and Thogotovirus.

SARS-CoV-2 receptor-binding domain bound to neutralizing antibody CB6 (PDB 7C01). Epitope in gold.
SARS-CoV-2 receptor-binding domain bound to neutralizing antibody CB6 (PDB 7C01). Epitope in gold.

Free energy & methods

We develop and test methods for estimating protein stability and binding free energies, from umbrella sampling and alchemical calculations to statistical models and neural networks that correct and quantify the uncertainty of FoldX predictions.

Ebola virus glycoprotein bound to antibody KZ52 (PDB 3CSY), one protomer shown. Binding interface in gold.
Ebola virus glycoprotein bound to antibody KZ52 (PDB 3CSY), one protomer shown. Binding interface in gold.

Drug & therapeutic design

We apply simulation and computational screening to therapeutic and agricultural problems, including enzyme inhibitors, bioactive milk peptides, engineered degron tags, and fungicide candidates for potato crops.

Cytochrome P450 17A1, a prostate cancer target, with the drug abiraterone (gold) above the heme (PDB 3RUK).
Cytochrome P450 17A1, a prostate cancer target, with the drug abiraterone (gold) above the heme (PDB 3RUK).

Microbes & protein evolution

We connect protein stability and binding to fitness and evolution in microbes, from bacteriophage and β-lactamase viability to yeast killer toxins and bacterial stress responses.

ϕX174 bacteriophage capsid (PDB 2BPA), with the G spike proteins in gold.
ϕX174 bacteriophage capsid (PDB 2BPA), with the G spike proteins in gold.

Tools & methods

  • GROMACS
  • CHARMM force field
  • FoldX / MD+FoldX
  • Umbrella sampling
  • Alchemical free energy
  • Steered MD
  • MM/PBSA
  • Machine learning (Python)
  • MDAnalysis
  • Blender + Molecular Nodes

Funding

Current support

  • National Institutes of Health (NIGMS), COBRE P20GM104420Institute for Modeling Collaboration and Innovation (IMCI, formerly CMCI), University of Idaho

Past support

  • National Science Foundation, EPSCoR RII Track-2 OIA-17362532019–2022

Computing resources

  • Research Computing and Data Services, Institute for Interdisciplinary Data ScienceUniversity of Idaho
  • IBEST Computational Resources Core (NIH P30 GM103324) and Idaho National Laboratory HPC Center2018–2022
  • NIH
  • IMCI
  • NSF
  • RCDS
  • IBEST
  • INL