We are biophysicists, chemists, biologists, and computer scientists, who address pressing questions in mechanisms of the cell signaling in health and disease. We develop multiscale computational methods and workflows by combining frameworks of molecular dynamics, quantum chemistry, and molecular evolution with multi-resolution experimental data. Current emphasis is on plasma membrane cell signaling, protein dynamics in complex environments, and functional lipids in membrane-associated phenomena.

Research Highlights

Majority of findings were achieved and/or verified in collaboration with experimental colleagues, including M. Gruebele, C. Rienstra, M. Burke, K. Hristova, J. Morrissey, and K. Zhang, among others.

Transmembrane signaling proteins: receptor tyrosine kinases

  • Funding: PI: NIH-R01 GM141298 2021/25, co-Is: Hristova & Zhang
  • Candidate structures of previously invisible RTK TM dimer structures (in progress)
  • Mutations play in EphA4 oligomerization and signaling (J. Biol. Chem, 2021)
  • Key side chains in binding of RTK TrkA juxtamembrane domain to membrane (JPCB, 2019

Functional lipid signatures & membrane-active agents

  • Funding: PI: NCSA CDDR (2021/23), co-I Kindratenko; co-I: NIH-tR01 GM123455 (2016/23),  PIs: Rienstra, Morrissey, Tajkhoshid
  • Cholesterol coupled dynamics in membrane (JACS, 2023)
  • Captured structures of anionic PS lipids shaped by Ca2+ in signaling (Biochem., 2018)
  • Capturing structure of the functional amphotericin B (AmB) – ergosterol sponge and development of safe AmB variant (Nature, 2023
  • Structure of the functional AmB sponge (Nat. Str. Mol. Biol., 2021)

In silico cell: dynamics in the crowd

  • Funding: key contributor: NSF 2205665 (2022/26), NIH-R01GM093318 (2017/21), PI: Gruebele
  • Perspective review article (JPCB, 2023)
  • Hinge-bending landscape of PGK in human cytoplasm (JPCL, 2024)
  • In-cell dynamics of ATP (JPCL, 2022)
  • Folding dynamics of diverse topologies – protein B (Prot. Sci., 2023) & WW domain (JPCB, 2020)
  • Protein-protein interactions are transient – a sign of quinary structure (JPCL, 2019)

Mechanisms of fast protein folding

  • Funding: key contributor: NSF 2205665 (2022/26), NIH-R01GM093318 (2017/21), PI: Gruebele
  • Small ubiquitous osmolyte TMAO protects proteins (Biophys. J., 2023)
  • Captured formation of a dry molten globule by a fast-folding protein (PNAS, 2019)
  • Differences in local and global probes of folding (JPCL, 2016)
  • Trap state captured and explored by a fast-folding protein (PNAS, 2015)