Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Benoit Roux Project Name: nachbac Division: BIO Project title: selectivity of the sodium channel Associated funding: NIH R01-GM062342 Other Systems: Science: Understanding quantitatively the microscopic factors giving rise to Na+ selective channels is mysterious. For a long while, we had only K+ selective channels (such as KcsA). Just recently, the X-ray structure of a Na+ selective channel was determined. It is related to the NachBAC channel (Na+ Channel from bacteria). Project description: The most informative strategy to address the issue of Na+ selectivity in NachBAC is to compute the multi-ion PMF corresponding to the microscopic process in question (Berneche and Roux, Nature 2001). In particular, the calculation of the PMF enables us to pin-point the location of the largest barrier opposing the passage of a single K+ ion relative to Na+ in the channel, thus explaining while the channel becomes selective from the free energy profile. We can carry those type of calculations using our new and highly scalable method called umbrella sampling with replica-exchange MD simulations that is implemented in CHARMM/REPD. We will compute the potential of mean force to ascertain the mechanism of ionic selectivity through the narrow pore. We need to compare permeation of Na+ (the good ion) against K+ (the bad ion). Thus, we need a 1-ion PMF for Na+ and for K+ going through the pore. And we need 2-ion PMF going through the pore because we do not know yet if the permeation mechanism is a one- or two-ion mechanism. For the 1-ion potential of mean force of Na+ through the channel: 60 windows/replica One replica use one node (8 cores). Sampling of 3 ns takes 150 hours. Total needed: 150*60*8 = 72,000 core-hours For the 1-ion potential of mean force of K+ through the channel: 60 windows/replica One replica use one node (8 cores). Sampling of 3 ns takes 150 hours. Total needed: 150*60*8 = 72,000 core-hours For the 2-ion potential of mean force with Na+ through the channel: 350 windows/replica One replica use one node (8 cores). Sampling of 1 ns takes 50 hours. Total needed: 50*350*8 = 140,000 core-hours For the 2-ion potential of mean force with K+ through the channel: 350 windows/replica One replica use one node (8 cores). Sampling of 1 ns takes 50 hours. Total needed: 50*350*8 = 140,000 core-hours analysis in 3 Qtr 3 * 25,000 GRAND TOTAL NEEDED: 500,000 core-hours. Project URL: http://thallium.bsd.uchicago.edu/RouxLab/ Current FY Hours Used: undetermined amount New FY Requested allocation: 500000 Q1: 425000 Q2: 25000 Q3: 25000 Q4: 25000 Justification: This is a very very competitive project, as others are racing to produce calculations. This is why our request is biggest at the early stage of the project. We are ready to proceed with these calculations as soon as we have the allocation. Thank You, The LCRC Accounts System