- Allocations-admins - mailman3.cels.anl.gov

New LCRC report submitted for cfd_enginemodeling
by support＠lcrc.anl.gov 21 Sep '10

21 Sep '10

Full project report at https://accounts.lcrc.anl.gov/reporting/project/index.pl?project=cfd_engine…

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New LCRC report submitted for cfd_enginemodeling
by support＠lcrc.anl.gov 21 Sep '10

21 Sep '10

Full project report at https://accounts.lcrc.anl.gov/reporting/project/index.pl?project=cfd_engine…

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[LCRC Accounts] Project Request: MINOTAUR
by accounts＠lcrc.anl.gov 21 Sep '10

21 Sep '10

Hello, A new project on the LCRC cluster has been requested. Please forward the information on to the LCRC Allocation sub-committee. Applicant's name: Ashutosh Mahajan Applicant's institution: ANL Applicant's division: MCS Project Name: MINOTAUR Project title: Next-Generation Solvers for Mixed-Integer Nonlinear Programs: Structure, Search, and Implementation Associated funding: DOE, through grant DE-FG02-05ER25694. Other Systems: None Science: One of our objectives in this project is to develop powerful algorithmic frameworks to solve previously intractable mixed-integer nonlinear programs (MINLPs). Another is to deliver implementations of these frameworks in new, publicly available solvers. Towards these ends, we are developing the solver MINOTAUR that can solve such problems found in many diverse applications. The difficulty and consequently, the solution time for these problems grow exponentially in the size of the input. Our objective is to harness the parallel processing machines to solve these problems in reasonable time. Another important part of this development is experimenting with many different algorithms and parameters in order to identify the best operating parameters based on the problem structure. Project description: We have developed over the last year, a solver named MINOTAUR, that can be used to solve medium size MINLP instances on a single processor. We are now in the stage of making it robust for ill posed problems and also adaptive to the type and structure of the problem. This effort requires extensive testing on a large set (over 300) of instances. Each test requires up to 500 core-hours and many such tests are required. While the first stage described above requires embarrassingly-parallel execution of several single-processor jobs, it is critical for the next stage of making MINOTAUR capable of harnessing distributed memory architectures. MINOTAUR solves MINLPs by a branch-and-bound methods, where the problem is divided recursively into smaller and smaller subproblems. Each subproblem is in turn a small MINLP that can be solved using the serial-processing techniques that have already been developed, but need tuning as described previously. The code being developed is written in C, C++ and Fortran. We are using MPI for the parallel implementation. I have already used my initial start-up allocation in some tests, and all the required libraries and code seem to compile and run fine. Project URL: Requested allocation: 50000 Justification: The requester has used 7519 hours of their initial startup project. In addition to approving an initial amount, please specify a Category and Subcategory for this project. For a list of the current selection of approved categories, please see: https://wiki.lcrc.anl.gov/wiki/Processes/Categories Once the Allocation committee has approved the project, please go to the Project Management page to create it: https://accounts.lcrc.anl.gov/projects.php Thank You, The LCRC Accounts System

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New LCRC report submitted for Comp_Nanocatalysis
by support＠lcrc.anl.gov 20 Sep '10

20 Sep '10

Full project report at https://accounts.lcrc.anl.gov/reporting/project/index.pl?project=Comp_Nanoc…

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New LCRC report submitted for Comp_Nanocatalysis
by support＠lcrc.anl.gov 20 Sep '10

20 Sep '10

Full project report at https://accounts.lcrc.anl.gov/reporting/project/index.pl?project=Comp_Nanoc…

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[LCRC Accounts] Yearly Allocation Request from RIA-RND
by accounts＠lcrc.anl.gov 19 Sep '10

19 Sep '10

Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Brahim Mustapha Project Name: RIA-RND Division: PHY Project title: Accelerator and Targets Simulations for the Rare Isotope Accelerator (RIA) facility. Associated funding: LDRD and DOE R and D funding for RIA Other Systems: AlCF Science: This project is two-fold: First, the simulation of different accelerator options for the future RIA facility in order to decide on the most performant and cost-effective option. Second, the simulation of targets to be used for the production of rare isotopes by the ISOL method (Isotope Separation On Line) in order to optimize the geometry and the arrangement of the target material for minimal losses of short-lived isotopes by radioactive decay. Project description: Most of the work proposed last year was postponed but we hope to do it this year: We plan to start simulations of the SNS linac now that the code is updated with all the required beam line elements. The advantage of simulating an existing machine is to be able to benchmark the code against experimental data. This should be a good step forward towards the realization of the concept of the model driven accelerator, that is using a realistic computer model for online machine operations. Project URL: http://www.phy.anl.gov/aebl Current FY Hours Used: undetermined amount New FY Requested allocation: 300000 Justification: Thank You, The LCRC Accounts System

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[LCRC Accounts] Yearly Allocation Request from batteryQC
by accounts＠lcrc.anl.gov 17 Sep '10

17 Sep '10

Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Jeff R. Hammond Project Name: batteryQC Division: LCF Project title: Quantum chemical simulations of batteries and related algorithms and software tools Associated funding: Argonne LDRD, Chemistry Exascale Codesign Center Other Systems: Intrepid/Surveyor: Blue Gene/P at Argonne (INF), Chinook: Opteron/IB at PNNL (8M), Jaguar: Cray XT5 at ORNL (?), Kraken: Cray XT5 at NICS/Teragrid (1M), Ranger: Opteron/IB at TACC/Teragrid (1M), Lincoln: Tesla/Xeon/IB at NCSA/Teragrid (100K), Dirac: Fermi/Nehalem/IB at NERSC (?), Hopper: Cray XE6 at NERSC (?), Palu: Cray XE6 at CSCS (?) Science: (1) quantum chemistry for metal-oxide systems related to battery science (2) statistical mechanics methods for non-equilibrium systems (3) communication runtime systems for HPC networks Project description: Accurate quantum chemistry methods, particularly coupled-cluster theory (CC), will be applied to metal oxide systems in order to understand the chemical properties of batteries. The CC method known CCSD(T) is often called the "gold standard" of quantum chemistry and provides the most accurate results available for a polynomial-scaling algorithm when applied to most chemical systems. In contrast, density-functional theory (DFT) cannot be used reliable for battery-like systems since localized electronic defects create problems for most of the approximate exchange-correlation functionals used today. This project seeks to calibrate quantum chemistry methods for battery-like systems and develop software to enable Argonne's computational investigations in battery science. The second component of this project is the development of massively-parallel non-equilibrium umbrella sampling (NEUS) algorithms (see http://code.google.com/p/parallelsampling) Alex Dickson and Aaron Dinner have developed a theory for this and Alex and Jeff have been implementing this algorithm in parallel using the Global Arrays toolkit. Both software development and applications will be performed using this allocation. We have a poster at Supercomputing 2010 poster accepted on the preliminary results of this work and have submitted an Argonne-UChicago Strategic Collaborative Initiative proposal to continue this work. We have been developing a new communication runtime system for Global Arrays and PGAS languages called OSPRI (formerly known as A1 - Argonne 1-sided - internally, see https://trac.mcs.anl.gov/projects/a1/) The implementation for Blue Gene/P over DCMF is essentially complete and we are now working on an implementation for commodity systems using MPI plus network-specific extensions (e.g. read-modify-write using IB Verbs). Because OSPRI is a drop-in replacement for ARMCI, we will be conducting performance tests of NWChem and Global Arrays using the new runtime. Experiments Planned: We continue to study lithium oxide clusters using coupled-cluster methods in collaboration with the Curtiss group at Argonne and to tune NWChem for Fusion for this and other purposes. The site installation of NWChem is maintained by the PI of this project and testing is conducted as part of this project, which benefits a number of researchers at Argonne. The NEUS experiments are designed by the Dinner group and involve: (1) evaluating the correctness of the NEUS algorithms for various systems, (2) optimizing hybrid MPI-OpenMP parallelism and (3) measuring parallel scalability over IB in comparison to BG/P. All OSPRI experiments are communication benchmarks of one-sided communication from the GA/ARMCI test suite as well as strong-scaling tests of NWChem. Programming Model and Scalability Issues: NWChem relies upon the Global Arrays (GA) library to provide a PGAS programming model which includes one-sided put/get/accumulate and dynamic load-balancing. Scalability issues appear only at the onset of data-starvation, but this is not critical, as efficient strong-scaling can be achieved over more than an order of magnitude variation in node-count, and greater strong-scaling could be achieved if low-end data was available (jobs are memory-bound). Software Requirements: NWChem requires MPI (C bindings only), the OpenIB stack, F77 and C compilers, and an optimized BLAS library. Performance Results and Efficiency of the Code: The NWChem CCSD(T) code hit 92% of theoretical peak on ~1000 Itanium CPUs on the old PNNL supercomputer and ~50% of theoretical peak on close to 100K CPUs of Jaguar. Flop-rate on BlueGene/P is 20-50% of peak due to the small number of registers, other memory limitations, and the absence of true RDMA capability on the BGP interconnect. This is a key motivation for using Fusion. Algorithmic developments are expected to improve the performance of non-BLAS3 operations, such as atomic integral generation. Job Characterization: We expect to run 12-24 hour jobs on 64-256 nodes for production runs and 1-2 hour jobs on 1-16 nodes for software development. While the fat nodes will be helpful in some cases, we are not dependent on them since NWChem scales to the full machine and no data is replicated. Other Information: The expected number of project members is approximately five. Jeff Hammond works on all aspects of the project. Alex Dickson works on NEUS. Jim Dinan will use this allocation for developing OSPRI if necessary. Jeff's summer interns use this project as necessary, but their consumption is nominal. Publications: Over the past six months, this project was used to generate results for the following papers: R. S. Assary, P. C. Redfern, J. R. Hammond, J. Greeley and L. A. Curtiss, Chem. Phys. Lett., accepted (2010). "Predicted Thermochemistry for Chemical Conversion of 5-Hydroxymethyl Furfural." R. S. Assary, P. C. Redfern, J. R. Hammond, J. Greeley and L. A. Curtiss, J. Phys. Chem. B, 114, 9002 (2010). "Computational Studies of the Thermochemistry for Conversion of Glucose to Levulinic Acid." The work on NEUS and OSPRI/A1 has been the subject of oral presentations and posters; conference and journal papers will be submitted in the next six months. Project URL: Current FY Hours Used: undetermined amount New FY Requested allocation: 200000 Justification: NWChem completely parallelized and scales to many thousands of CPUs. The communication mechanism, ARMCI, has been extensively optimized for Infiniband and provides one-sided performance very close to the hardware capacity. The particularly methodology to be used for this project, CCSD(T), is implemented two different ways in NWChem, one of which scales at >90% efficiency from 1024 to 6144 CPUs on the Chinook supercomputer, which is very similar to Fusion, except larger. The other implementation hit ~0.5 PF on 96K cores of JaguarPF and is the basis for a Gordon Bell Finalist by another group of NWChem developers. The serial kernel in CCSD(T) is DGEMM, which should hit 90% of machine peak using Intel MKL. Performance analysis on both Surveyor and Chinook indicate that DGEMM is >50% of the wall time for large jobs and the rest can be tuned to achieve ~10% of theoretical peak. Hence, these should run at ~50% of theoretical peak (50%*90%+50%*10%=50%). The motivation to use Fusion instead of other machines I have access to is that most jobs are memory-bound, so BlueGene/P is not ideal, and the operating systems on both Chinook and Jaguar are unreliable at scale. The NEUS code scales from 1 to 8K cores of BG/P with 99% efficiency. The hybrid parallelism using OpenMP is near perfect on BG/P within a node. On Fusion, we expect less efficient thread parallelism but nonetheless, NEUS will run on the entire Fusion machine if necessary. OSPRI aka A1 has been tested extensively on BG/P and is, by design, almost scale-free. Thank You, The LCRC Accounts System

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[LCRC Accounts] Yearly Allocation Request from kcsa
by accounts＠lcrc.anl.gov 17 Sep '10

17 Sep '10

Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Benoit Roux Project Name: kcsa Division: BSD Project title: Computational study of ion selectivity in the KcsA channel Associated funding: NIH-GM062342 Other Systems: NCSA, KBT Science: The selective binding of small ions (e.g., Na+, K+, Ca2+, Mg2+) to protein sites plays a key functional role in many important biological processes. The selectivity for is governed by the free energy landscape encountered by the different ions when they associated with the binding site. This, in turn, reflects the balance of ion-protein and ion-solvent interactions. Project description: Understanding quantitatively the microscopic factors controlling ion selectivity remains a great challenge. In simple terms, the concept of selectivity means that the "correct" ion, is able to binding more favorably than an "incorrect" ion. At a physical level, it is to be anticipated that energetics and solvation play a key role in this process, although different aspects of energetics may be highlighted by the various experimental methods used to probe the system. Some experimental measurements are more sensitive to the relative depth of free energy wells, while others are more sensitive to the relative height of free energy barriers. In the case of ion channels, the large hydration energy of the ions contrasts with the small free energy barriers necessary for the fast conduction observed experimentally. This implies that ion-protein association is ultimately controlled by a delicate balance of very strong interactions. Frequently, permeation invo lves the partial dehydration of an ion, followed by the binding to a proteinaceous environment. This archetype is well illustrated by the crystal structure of the KcsA channel. The pore of the KcsA channel comprises a wide aqueous vestibular entryway, lined by non-polar residues on the intracellular side, leading up on the extracellular side to a narrow region lined by backbone carbonyl oxygens. This region of the pore, formed by the residues corresponding to the signature sequence TTVGYG common to all K+ channels, acts as a "selectivity filter" by allowing only the passage of nearly dehydrated K+ ions across the cell membrane. In such narrow molecular pores, a permeating ion must shed most of its surrounding water molecules and the large energetic loss due to dehydration must be compensated by coordination with the backbone carbonyl oxygens. The most informative strategy to address such issues 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 Na+ ion while there are two K+ ions elsewhere in the pore. We carry those type of calculations using umbrella sampling MD simulations. Another strategy is free energy perturbation (FEP), which allows to compute the relative free energy of different ions at precise location in the pore. There are 2 sub-projects: 1) Compute the multi-ion PM for Na+ permeation through the KcsA channel using the open state structure that was recently determined by X-ray crystallography in the Perozo laboratory. We have already done a similar calculation for the KcsA in the closed state (Egwolf and Roux, JMB 2010). Umbrella sampling MD simulations are used to obtain W(z1,z2,z3) the 3-ion PMF function of the coordinate of the 3 ions in the selectivity filter. To understand the effect of selectivity, two systems must be considered: with 3 K+ ions, and with 1 Na+ and 2 K+ ions. Based on our experience with similar computations, we know that a grand total of 3931 MD window simulations is needed for two systems. Each window should be simulated for 0.6 ns, the first 0.1 ns being used for equilibration and the last 0.5 ns for sampling proper, for total aggregate MD simulation time of 2.4 microseconds for each of the two systems. The unbiased 3D PMFs are then calculated using the weighted histogram method ( WHAM). The simulations are generated with NAMD, which is the most efficient program for classical MD. 2) Use FEP to compute the relative free energy of Na+ and K+ in a KcsA pore with DFT/MM simulations. For this computation we are using CHARMM combined with the DFT program DEMON (developed by Denys Salahub in Calgary). This enables us to treat the ions and the nearby protein atoms with DFT and the remainder with the force field of molecular dynamics. Software requirements NAMD, CHARMM, DEMON Expected number of project members: Benoit Roux, David Medovoy (multi-ion PMF calculation) and Chris Rowley (selectivity with density function theory and MD force field) REFERENCES Noskov, SY; Berneche, S; Roux, B Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands. NATURE Volume: 431 Issue: 7010 Pages: 830-834 Published: OCT 14 2004 Egwolf, B; Roux, B Ion Selectivity of the KcsA Channel: A Perspective from Multi-Ion Free Energy Landscapes. JOURNAL OF MOLECULAR BIOLOGY Volume: 401 Issue: 5 Pages: 831-842 Published: 2010 Project URL: http://thallium.bsd.uchicago.edu/RouxLab/research.html Current FY Hours Used: undetermined amount New FY Requested allocation: 100000 Justification: The umbrella sampling calculations described here constitute a major part of the PhD thesis of David Medovoy, a graduate student in Biophysics at the University of Chicago. The total requested allocation for this project is: 500,000 SU = (3931 windows) * (0.6 ns/window) * ((8*cores)*(12 hour)/ns). The planned FEP simulations for with DFT/MM will be carried out by Chris Rowley, a postdoc in the lab who has a fellowship from the Canadian NSERC. His work will be a new attack on the problem. Never before has someone computed relative free energies in those channels with DFT/MM. We anticipate this those FEP calculations will require about 500,000 SUs during the year. Demon scales up to about 64 processors, but we are investigating the dependencies on grid density (in DFT) to see how it affects the performance. Thank You, The LCRC Accounts System

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[LCRC Accounts] Yearly Allocation Request from Drude
by accounts＠lcrc.anl.gov 17 Sep '10

17 Sep '10

Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Benoit Roux Project Name: Drude Division: BIO Project title: Development and validation of new polarizable force field for molecular dynamics Associated funding: LDRD: 2009-047-R1, "Novel Computing Methodologies for the Simulation of Complex Molecular Systems" NIH grant from NIGMS R01-GM072558: Polarizable Force Field For Proteins and Lipids Other Systems: BG/P, NCSA, PSC, KBT Science: The functional form and parameters of a new force field accounting for induced polarization in molecular dynamics simulations must be developed, optimized, and validated for various biomolecular systems. Project description: At the present time, MD simulations are not only limited by the computational resources but also by the physical correctness and accuracy of the underlying atomic models. Without a systematic approach to generate, test and validate the accuracy of the force fields, the value of MD simulations will always remain in question. The development of potential functions for computer simulations has a long history and is still a very active field. Essentially all of the MD simulations of complex molecular systems (biological or not) are currently carried out using fixed-charge non-polarizable force fields, even though there is a broad consensus that electronic polarization effect ought to be included. The important role of polarization is particularly obvious for self-assembling amphiphilic molecules, containing polar or charged groups as well as nonpolar moieties (see below). A number of research groups are working at developing new algorithm to treat polarizati on, either with inducible point dipoles, fluctuating charges, or classical Drude oscillators. The latter approach, which we have adopted, is the most advantageous due to its simplicity and computational efficiency. The goal is to develop, optimize, and validate the functional form and parameters of a new force field accounting for induced polarization in molecular dynamics simulations. We are particularly interested in ion solvation properties. # computational methods The computational method involves ab initio quantum mechanics, as well as classical molecular dynamics simulations and free energy perturbation. The induced polarization is represented by introducing a small auxiliary charged particle attached to the nucleus by a spring. The pair forms a Drude oscillator. It can be shown that this construction accounts properly for the physics of induced polarization in molecular interactions. # scalability issues The new force field is developed to be implementable in a wide range of existing molecular dynamics codes. Currently, the model is supported by CHARMM, which has modest scalability. Our initial implementation of the methods in NAMD has allowed to run some benchmark systems with 75,000 water molecules with the polarizable force field. These NAMD simulatinos scale up to 1,000 cores without problems. # experiments planned We are also developing ion solvation models in water, liquid N-methylacetamide, and liquid ethanol. Those are needed to model biomolecular systems. The work will comprise - divalent ions solvation in N-methylacetamide - CPMD run of K+ in ethanol - CPMD run of Na+ in ethanol - high level ab initio on small clusters - free energy perturbation MD of K+ in ethanol - free energy perturbation MD of Na+ in ethanol - osmotic pressure MD for NaCl and KCl - conductivity of KCl and NaCl # software requirements We use Gaussian, Qchem, CPMD, CHARMM, and NAMD. # sizes of calculations run on and/or planned for Fusion or other systems On single MD runs, we expect to use up to 256 or 512 cores in parallel. The CPMD does not scale as well (perhaps up to 64). The FEP simulations are trivially distributed (thermodynamic integration). The osmotic pressure and the conductivity require several MD at increasingly high ionic concentrations with large systems. # expected number of project members: The number of members is expected to be 5-6, including Benoit Roux, Karen Callahan (ions in ethanol), Yun Luo (osmotic pressure), Chris Rowley (divalent ions), from the University of Chicago. REFERENCES Yu, H; Mazzanti, CL; Whitfield, TW, et al. A Combined Experimental and Theoretical Study of Ion Solvation in Liquid N-Methylacetamide. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Volume: 132 Issue: 31 Pages: 10847-10856 Published: 2010 Baker, CM; Lopes, PEM; Zhu, X, et al. Accurate Calculation of Hydration Free Energies using Pair-Specific Lennard-Jones Parameters in the CHARMM Drude Polarizable Force Field. JOURNAL OF CHEMICAL THEORY AND COMPUTATION Volume: 6 Issue: 4 Pages: 1181-1198 Published: 2010 Yu, HB; Whitfield, TW; Harder, E, et al. Simulating Monovalent and Divalent Ions in Aqueous Solution Using a Drude Polarizable Force Field. JOURNAL OF CHEMICAL THEORY AND COMPUTATION Volume: 6 Issue: 3 Pages: 774-786 Published: 2010 Harder, E; MacKerell, AD; Roux, B Many-Body Polarization Effects and the Membrane Dipole Potential. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Volume: 131 Issue: 8 Pages: 2760-+ Published: 2009 Harder, E; Anisimov, VM; Whitfield, TW, et al. Understanding the dielectric properties of liquid amides from a polarizable force field. JOURNAL OF PHYSICAL CHEMISTRY B Volume: 112 Issue: 11 Pages: 3509-3521 Published: 2008 Whitfield, TW; Varma, S; Harder, E, et al. Theoretical study of aqueous solvation of K+ comparing ab initio, polarizable, and fixed-charge models. JOURNAL OF CHEMICAL THEORY AND COMPUTATION Volume: 3 Issue: 6 Pages: 2068-2082 Published: 2007 Project URL: http://thallium.bsd.uchicago.edu/RouxLab/ Current FY Hours Used: undetermined amount New FY Requested allocation: 300000 Justification: We have an excellent track record of publication in this field, and we will make good use of the allocated time. The project involves a variety of different computations (MD, ab initio, CPMD), which are all very important to develop good models. We could easily ask for more resource, and we will definitely utilize all the allocation requested. Thank You, The LCRC Accounts System

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[LCRC Accounts] Project Allocation Request
by accounts＠lcrc.anl.gov 17 Sep '10

17 Sep '10

Hello, A change in allocation has been requested: Requester: roux (Benoit Roux) Project: kv Title: Studies of voltage-vgated potassium channel Description: Voltage-gated potassium (Kv) channels are membrane proteins that respond to changes in the transmembrane potential by altering their conformation to allow the passive conduction of K+ ions across the cell membrane. These channels are tetrameric proteins, in which each subunit comprises six transmembrane (TM) helical segments (S1-S6). The ion conduction pore is located at the center of the tetrameric structure and is formed by the S5 and S6 helices from the four subunits. The first four segments (S1-S4) in each subunit form a voltage-sensing domain (VSD) that is located in the lipid membrane at the periphery of the central pore domain (PD). Upon depolarization of the membrane, the VSD in each subunit undergoes a voltage-dependent transition from a resting to an active conformation, which then leads the opening of the intracellular gate of the ion conduction pore. The conformational changes associated with the activation of Kv channels result in the transfer of an electric charge Delta-Q across the membrane, that can be measured experimentally as a small transient capacitive current. In the Shaker K+ channel, the "gating charge" corresponds to the transfer of 12-14 elementary charge (e) along the transmembrane electric field. Correspondingly, a change V in the membrane potential shifts the relative free energy of the closed and open conformations by V*Delta-Q. The gating charge DeltaQ is, thus, a key concept to explain how channel activation is coupled to the membrane potential. Initially postulated by Hodgkin and Huxley in 1952, it was first detected and measured more than 20 years later by Armstrong and Bezanilla. Ultimately, explaining the voltage-gating mechanism of Kv channels in molecular terms requires gaining knowledge of the active and resting conformations, and then showing how those conformations are able to account for the experimentally observed gating charge Delta-Q. Our strategy is to first carefully construct atomic models of the active and resting states of Kv channels that are consistent with all available experimental information using protein structure prediction algorithms. We also have a novel method to compute the gating charge using all-atom MD. Pathak et al. have generated detailed atomic models of Kv1.2 in the open/active and closed/resting states using the Rosetta-Membrane structure prediction program. The model of the open/active state complements the information missing from the X-ray structure of the Kv1.2 channel used as a template, while the S1-S2, S2-S3, and S3-S4 loops in the voltage sensing domain were modeled de novo. These results offer a promising starting point to expand our understanding of voltage gating in Kv channels. Some critical issues must be addressed. Recently, the stability of those structural models in the complex dynamical environment of the lipid bilayer was ascertained using molecular dynamics (Khalili-Araghi et al, 2010) and the gating charge was calculated using a new theory of the membrane potential (Roux, 2008). Our long-term goal is to refine the atomic models of the closed/resting and open/activated states and test their ability to account for the experimentally observed gating charge using all-atom MD and explicit lipid membrane environment. In the coming year, we have 3 specific sub-projects: 1) We want to incorporate additional experimental constraints in the refinement of the resting down-state of the voltage sensor (Macpos et al, 2007). Ernesto Vargas (a graduate student at the University of Chicago) is carrying out this project. 2) We want to predict the effect of side-directed mutations on the channels, namely the effect of substitution along the transmembrane helix S4. David Medovoy (a graduate student at the University of Chicago) is carrying out this project. 3) We want we want to refine the 3d structure of the bacterial voltage-gated channel KvAP using electron paramagnetic resonance (EPR). We will use a new mmethod that has been develop by us (Sompornpisut et al, 2008) and tested on other channels (Vasquez et al, 2008). This work will be carried out by a visiting scholar (Rong Shen). We had originally requested 250K nodehours for the fiscal year, but only half of that, 125K was granted by the Allocation committee. These systems run NAMD on 25 cores at a rate of about 1 day/nanosecond of MD. For a total of 50 ns of simulation total for the 3 projects means that we need about 300,000 nodehours. REFERENCES Pathak, M.M., V. Yarov-Yarovoy, G. Agarwal, B. Roux, P. Barth, S. Kohout, F. Tombola, and E. Y. Isacoff. (2007). "Closing in on the Resting State of the Shaker K+ Channel." Neuron 56, 124-140. Campos, F.V., B. Chanda, B. Roux, and F. Bezanilla. (2007). "Two Atomic Constraints Unambiguously Position the S4 Segment Relative to S1 and S2 Segments in the Closed State of Shaker K Channel." Proceedings of the National Academy of Sciences of the United States of America 104, 7904-7909. Sompornpisut, P., B. Roux, and E. Perozo. 2008. Structural refinement of membrane proteins by restrained molecular dynamics and solvent accessibility data. Biophys 95:5349-5361. Vasquez, V., M. Sotomayor, D. M. Cortes, B. Roux, K. Schulten, and E. Perozo. 2008. Three-dimensional architecture of membrane-embedded MscS in the closed conformation. J Mol Biol 378:55-70. Pan, A.C., D. Sezer, and B. Roux. (2008). "Finding Transition Pathways Using the String Method with Swarms of Trajectories." J Phys Chem B 112, 3432-3440. Roux, B. 2008. The membrane potential and its representation by a constant electric field in computer simulations. Biophys J 95:4205-4216. Khalili-Araghi, F., V. Jogini, V. Yarov-Yarovoy, E. Tajkhorshid, B. Roux, and K. Schulten. 2010. Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel. Biophys J 98:2189-2198. Current: undetermined amount Justification: We had originally requested 250K nodehours for the fiscal year, but only half of that, 125K was granted by the Allocation committee. These systems run NAMD on 25 cores at a rate of about 1 day/nanosecond of MD. For a total of 50 ns of simulation total for the 3 projects means that we need about 300,000 nodehours. For the resources, we expect to be using NAMD runs of up to 256 CPU. This amounts to: 256 CPU * 24 hours * 50 days = ~300,000 Fusion will be an excellent platform to establish and execute the string method algorithm. Requested: 300000 A specific reason has been given: Allocation will enable the computations required for the 2 sub-projects. This needs to be approved and the final allocation amount decided upon. Thank You, The LCRC Accounts System

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