Hello, A change in allocation has been requested: Requester: leaf (Gary Leaf) Project: dynamics Title: Dynamics of biophysical systems. Description: The goal of our computations for the reduced model of a sodium channel is to compute the dependence of the free energy components for the channel. We investigate the dependence on such factors as channel size, cation size in relation to channel size, ion charge, protein polarization effects, and polarization effects in the channel. The object is to gain a deeper understanding of the selectivity mechanism whereby some ions are selected over others for transport through the channel. This is in spite of the difference in concentration outside the channel. Our computations are based on using a Grand Canonical Monte Carlo (GCMC) scheme to compute the free energy components as well as the expected ionic concentration in the filter portion of the channel. For a given state (configuration and parameter settings) we compute a multiple set of final realizations in parallel. The number of realizations ranges from 24 to 48 with 32 being the usual number. We expect each GCMC calculation will require on the order of 40K steps with 50-70 particle insertion/deletion attempts as part of the free energy calculation. Our computational study will divided into three main segments. Each segment has three parts that are essentially the same for each segment. Segment I. Here we model with a homogeneous dielectric; so that there is no polarization effects from either the protein or the or the channel. The object is to isolate the effect of excluded volume on selectivity. Because this model is homogeneous, the computations are relatively short. On the order of 8 hours per calculation. Part A. Vary the filter pore radius: R = 3.0 3.5 4.0 4.5 5.0 Angs Part B. Vary the type of cation competing with sodium. Part C. Study the transmission of sodium over calcium for a sodium channel by gradually titrating calcium into the system. Because the this model homogeneous, the computations are very modest. We estimate that the study for segment I will require on the order of 4000 core-hours using 32 cores per computation. Cost: 4000 core-hours for Segment I study. Segment II. Study the role of protein polarization by varying the protein dielectric. This model is inhomogeneous, hence considerably more computationally expensive. This study has the same three parts as Segment I, but more calculations for each part as well as the increased cost of each run. We estimate that this portion of the study will involve about 60 cases covering the parameter ranges. Using 32 cores, although 48 may be needed, each will require on the order of 1664-2496 core-hours. Based on 60 cases this yields Cost : 99840-149760 core-hours for Segment II study Segment III. Study the role of polarization in the sodium channel by varying the channel dielectric. These cases also involve an inhomogeneous model; thus the cost will be comparable to the cost of the study in Segment II. Cost : 99840-149760 core-hours for Segment III study. Current: undetermined amount Justification: Requested: 90000 A specific reason has been given: Our allocation for the 1st half of the year is nearly exhausted. We've used approximately 45K per month on average so far this FY; continuing at that rate, we will require another 90K for the remainder of the current quarter. This needs to be approved and the final allocation amount decided upon. Thank You, The LCRC Accounts System