Mechanisms of allostery and regulation in glycolysis

Glycolysis is a key metabolic pathway, forming a starting point of several other important pathways. As such, it is subjected to extensive regulation allowing it to respond to the cell’s varying demands of energy and building blocks. However, molecular details of this complex regulation are still not fully understood. In this work, the PhD student will use a variety of computational approaches, including molecular dynamics simulations coupled with enhanced-sampling techniques, to elucidate the mechanisms of allosteric regulation of glycolysis by cellular energy signals. A focus of the work will be on PFK1, a rate-limiting enzyme forming a “gatekeeper” of glycolysis. The work will benefit from the currently expanding set of available structural data of glycolytic enzymes, including data obtained by our experimental collaborators.