A New Model of the Mitochondrial Pyruvate Carrier

Pursuit of Mitochondrial Pyruvate Carrier (MPC) characterization has been ongoing since the early 1970's. Occupying a central position at the junction of several metabolic and anabolic processes, with potential roles in various regulatory mechanisms, accurate modeling of MPC structural features offers much potential for such applications as the engineering of drought tolerant crops via stomatal regulation. Since the discovery of the genetic sequences encoding the MPC in 2012, research has blossomed. Perhaps as much has been written on the subject in the past three years as in the preceding three decades. Here, a new model of the MPC1- MPC2 heterodimer from A. thaliana is presented. MPC1 and MPC2 monomers were generated by multi-template-based homology modeling via the I-TASSER web server. MPC1 is joined to MPC2 by the pyDock web server. A series of pyruvate binding sites are computed through AutoDock Vina. Refinements were made to the pyruvate- MPC interactions by the Rosetta Ligand Docking Protocol. Assessments of the model were made against the current literature. The prevailing design of this project has been an empirical exploration, and attempts have been made to minimize the placement of directed emphasis in pursuit of specific ends. Rather, assumptions and processes built into the various algorithms guide construction at each step. The hope is that the results are somewhat more organic than reductive. That the resulting product is in concert with many key predictions made in the wet labs offers some support to our methodological decisions.