My work in Dr. Sukharev's lab started with patch-clamp studies of wild type and truncated mutants of MscL, and gradually developed to involve more kinetic and thermodynamic analysis of the channel behavior. This analysis allows to extract spatial and energetic characteristics of different states of the channel that are crucial for building the structural models of the gating. In the case of wild type MscL and Gain-of-Function MscL mutants it enabled us to provide thermodynamic description and confirm spatial parameters of the MscL gating scheme developed in collaboration with Dr. H. Robert Guy. As for MscS, this approach - combined with steered molecular dynamics - allowed us to come up with the gating scheme involving opening, closure and tension/voltage-dependent inactivation of the channel.
During the last three years we've been using an increasingly larger amount of molecular dynamics simulations in order to predict protein domains stability and hydration state of the pore as well as to suggest models of the different conformational states of the channel and to reconstruct the gating pathway between them. Currently this is my primary interest and responsibility. The collaborative atmosphere in our lab and the coexistence of computational and experimental approaches gives us a unique opportunity to experimentally test predictions derived from simulations. Those immediate experimental tests, in turn, allow to correct the models and refine experimental designs.
I am also involved in a collaborative project with Dr. Marco Colombini dealing with a simulational search of the molecular basis for the formation of ceramide channels. These channels can be observed experimentally in planar lipid bilayers and liposomes, and are supposed to permeabilize mitochondrial membranes, the process crucial to apoptosis initialization.
During my work on this project, I developed several applications in MatLab,
which can be found here:
Additionally, I wrote a number of scripts for VMD (the program for molecular visualization and analysis created in Dr. Klaus Schulten's lab). The scripts can be downloaded here. Custom syntax files for Crimson Editor, allowing highlighting Tcl/Tk language in the VMD/NAMD variant are also available.