Abstract: Mitochondria, often called the “powerhouse of the cell”, are membrane-enclosed compartments found inside nearly all eukaryotic cells. Their primary responsibility is to convert adenosine diphosphate (ADP) to adenosine triphosphate (ATP) - a small molecule that is the main source of energy for all cellular activity. The voltage-dependent anion channel (VDAC) is a protein that resides in the outer membrane of the mitochondria, and it forms the primary pathway for ADP to enter the mitochondria and ATP to exit. In the open state, more than one million ATP molecules can flow through a single VDAC channel, while the closed state blocks ATP permeation. VDAC has been studied experimentally for over 30 years, but only in the past few years have researchers determined its three dimensional structure. In this talk, I will discuss our molecular simulations of VDAC in the presence of ATP to determine if the recently solved structures represent the open or closed state. Unfortunately, ATP permeation occurs on the multi-microsecond timescale, while most molecular simulations last 10-100 nanoseconds. I will discuss our use of Markov State Models to bridge these timescales by piecing together information from hundreds of short simulations to determine the long time transport behavior of the channel.About Dr. Grabe: Prof. Grabe completed his undergraduate degree in mathematics-physics at Brown University and then went on to obtain his PhD in physics from UC Berkeley. He worked with Prof. George Oster at Berkeley using computational methods to study the rotary molecular motors V-ATPase and F-ATPase. In 2002 he joined Prof. Lily Jan’s group at UC San Francisco where he studied aspects of potassium channel structure and function such as ion selectivity and channel opening. In 2006 Prof. Grabe moved to the Department of Biological Sciences at the University of Pittsburgh as an Assistant Professor where he continued to use computational methods to explore the function of ion channels and transport proteins. In 2012 he was promoted to Associate Professor, and he is currently a visiting professor at UC San Francisco.
For more information, please call Amandi Machi at x6155.