Monday, April 15, 2013

Next Meeting: Tuesday, April 23, 2013 at 3:00 in 3065 BST3 (conference room)

Topic: Kinetic Proofreading - how the cell uses free energy to increase fidelity of translation.  We'll study a sample mechanism describing the exchange of free energy for information.

Reading: Uri Alon, An Introduction to Systems Biology, Chapter 9.  Contact me if you need a copy of the necessary pages.

More information: http://biops-pgh.blogspot.com/

Friday, April 5, 2013

Meeting Summary - Tuesday, Feb 19, 2013

What was scheduled ...

Topic: Free energy transduction via molecular machines.  Review of how free energy is stored and, qualitatively, transduced.  Introductory quantitative analysis of free energy transduction.

Reading: TL Hill, "Free energy transduction and biochemical cycle kinetics," Chapter 1.  This is a classic book, and chapter 1 is essential reading, nicely presented.  The rest of the book is more opaque.  The book is available cheaply in a Dover edition.  Let me know if you will not have access to a copy.

Summary
Hill's first chapter illustrates free energy transduction using a number of simple models.  The models have discrete states and simple first order kinetics - such as (i) a transporter being open to one side of a membrane or the other and being bound to ligands or not or (ii) a cycle involving binding of a substrate, catalysis, and unbinding of the product.  Every model includes one or more cycles because the proteins are re-used.  Hill identifies simple cycles (involving, for instance, binding and unbinding of a single ligand) and more complex cycles (involving, say, multiple species).

The chapter analyzes how free energy is "transduced," or transferred from one form to another.  An example of transduction is when the gradient of one type of molecule (across a membrane) is used to drive the creation of a gradient in another molecule.  Such gradients, which are out of equilibrium, store free (i.e., usable) energy.  The chapter shows that it is the complex cycles, which couple one process to another (e.g., the transport of two types of molecules), that can transduce free energy.  Simple cycles involving a single species only facilitate - really, catalyze - moving from a high free energy non-equilibrium state (e.g., gradient of A across a membrane) to an equilibrium state (matching concentrations of A on both sides of the membrane).  Effective molecular machines are those which have tightly coupled complex cycles and ineffective (i.e., slow) or inoperative simple cycles.