This work was performed under the auspices of the U.S. Department of Energy (DOE) by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Los Alamos National Laboratory (LANL) under Contract DE-AC5206NA25396, Oak Ridge National Laboratory under Contract DE-AC05-00OR22725, Argonne National Laboratory under Contract DE-AC02-06-CH11357, and FNLCR under Contract HHSN261200800001E. Release: LA-UR-19-32061, LLNL-JRNL-799963. We thank Siewert-Jan Marrink and Carsten F.E. Schroer for advice on Martini and GTP parameters, and Matt Drew, Shelley Perkins and Vanessa Wall from the National Cancer Institute (NCI) RAS Initiative, Jeff Clogston from Nanotechnology Characterization Laboratory, and Will Heinz from Optical Microscopy Analysis Laboratory, Frederick National Laboratory for Cancer Research (FNLCR), for cloning, expression and protein purification. >/p>
This work has been supported in part by the Joint Design of Advanced Computing Solutions for Cancer (JDACS4C) program established by the U.S. DOE and the NCI of the National Institutes of Health. We thank the Livermore Institutional Grand Challenge and LANL Institutional computing for computing time. The LANL Institutional Computing Program is supported by the U.S. DOE National Nuclear Security Administration under Contract No. DE-AC52-06NA25396.
C.N., F.C.L., F.D.N., G.D., H.B., H.I.I., J.N.G., L.G.S., M.P.S., P.T.B., S.G., S.I.L.K.S., Sh.S., T.O., T.S.C. and X.Z. contributed to the multiscale framework. C.A.L., C.N., H.I.I., T.S.C., Ti.T., X.Z., Y.Y. performed MD simulations. A.A., A.F.V., A.M., B.C.V.E., C.A.L., C.N., F.C.L., G.D., H.B., H.I.I., J.J.H., N.W.H., P.T.B., S.G., S.I.L.K.S., S.L., Su.S., T.O. and T.S.C. analyzed simulations. A.G.S, C.A., D.C., D.G., D.K.S., F.J.F., G.G., Q.N.V., R.S., T.H.T. and Th.T. performed and/or analyzed experiments. A.A., A.G.S, A.M., A.R., C.A.L., C.N., D.G., D.K.S., D.V.N., F.C.L., F.D.N., F.H.S., F.M., G.D., G.G., H.B., H.I.I., J.J.H., J.N.G., L.G.S., N.W.H., P.T.B., R.S., S.G., S.I.L.K.S., S.L., Su.S., T.O., T.S.C., Th.T., X.Z. and Y.Y. contributed to design and wrote the manuscript.
F.M. is a consultant for AduroBiotech, Amgen, Daiichi Ltd., PellePharm, Pfizer, Inc., PMV Pharma, and Portola Pharmaceuticals. F.M. is a consultant for and cofounder of Avidity, BridgeBio, KGen, and Quartz.
Data and materials availability:
All macro and micro simulation input and parameter files with an example micro simulation are available at https://bbs.llnl.gov/xxx.html
. Simulation data will be made available upon reasonable requests, size of all raw data is hundreds of TB.
MuMMI is composed of numerus sub-components both freely available 3rd party applications and custom codes; of those ddcMD (github.com/LLNL/ddcMD), ddcMDconverter (github.com/LLNL/ddcMDconverter), Maestro (github.com/LLNL/maestrowf), and Flux (github.com/flux-framework) are already available open source.