Our group specializes in theoretical computational modeling of structure-function relationships in biological macromolecules, such as proteins, lipids and RNA.
I. We study multiple aspects of ion selectivity and permeation, allosteric mechanisms of gating and drug modulation in ion channel and receptor proteins.
These proteins are typically constructed as multi-subunit assemblies.
Each subunit may in turn consist of several structurally and functionally distinct domains assembled in a modular fashion.
One example is an ionotropic glutamate receptor (iGluR), which is built as a tetramer in which a bundle of alpha-helixes spans
lipid bilayer (biological membrane) to form a water-filled channel for ion permeation.
The channel is gated (opens and closes) when ligand molecules, such as an agonist glutamate,
bind to the extra-cellular ligand binding domains of the protein.
Transmission of a gating signal from the ligand binding site to the transmembrane domain is not well understood.
To model function of a biological channel we are developing theoretical models and methodologies, which combine molecular level description of the protein
and a coarse grained description of protein domains on a micro- to millisecond time-scales relevant to the physiological function.
II. We utilize molecular modeling and simulation techniques to predict free energies of small molecule binding and macromolecule conformational rearrangements.