Uncovering the Elusive HIV Capsid with Kepler GPUs Running NAMD and VMD
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Computational scientists at the University of Illinois at Urbana–Champaign and the University of Pittsburg have now resolved the HIV capsid's chemical structure. As reported recently on the cover of Nature, the researchers combined NMR structure analysis, electron microscopy and data-guided molecular dynamics simulations utilizing VMD to prepare and analyze simulations performed using NAMD on NVIDIA GPUs in one of the most powerful computers worldwide, Blue Waters, to obtain and characterize the HIV-1 capsid. The discovery can now guide the design of novel drugs for enhanced antiviral therapy.Also learn how NAMD performs with the latest Kepler GPUs, as well as details about GPU Test Drive (www.nvidia.com/GPUTestDrive) and how to try NAMD on Kepler GPUs for free.
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Uncovering the Elusive HIV Capsid with Kepler GPUs Running NAMD and VMD
- 1. GPU Accelerated Apps Momentum Key codes are GPU Accelerated! Molecular Dynamics Abalone – GPU only code ACEMD – GPU only code AMBER CHARMM DL_POLY GROMACS HOOMD-Blue – GPU only code LAMMPS NAMD Quantum Chemistry ABINIT BigDFT CP2K GAMESS Gaussian – in development NWChem Quantum Espresso TeraChem – GPU only code VASP Check many more apps at www.nvidia.com/teslaapps
- 2. Test Drive K20 GPUs! Experience The Acceleration Run NAMD on Tesla K20 GPU today Sign up for FREE GPU Test Drive on remotely hosted clusters www.nvidia.com/GPUTestDrive
- 3. Unveiling the structure of the HIV-1 capsid Juan R. Perilla http://www.ks.uiuc.edu Theoretical and Computational Biophysics Group University of Illinois at Urbana-Champaign
- 4. HIV Replication Cycle - Overview Source: NIAID/NIH
- 5. Structure of the HIV capsid Pentamers introduce sharp declinations Continuously changing curvature in the hexagonal lattice Highly schematic model; beads are not proteins! Ganser, B. K. (1999). Science, 283, 80–83 Capped fullerene cone Briggs, J. et al. (2006). Structure, 14, 15–20
- 6. X-ray structure of CA Obtained Through Ingenious Preparation increase concentration Pornillos, O. , Sønquist, et al. (2009). Cell, 137(7), 1282–92.
- 7. Structure of Full Length CA NTDs and CTDs play different roles C-terminal domain hexameric center trimeric center There are also dimeric symmetry centers! N-terminal domain hexamer CA-hexameric planar lattice in crystal NTD fills inside space of hexamers, CTD fills outside. Ganser-Pornillos, B. K. et al. (2007). Cell, 131(1), 70–9.
- 8. Cryo-EM maps of the HIV Capsid in vitro, 1 M NaCl Cryo-EM micrograph of recombinant WT HIV-1 CA at 8 Angstrom
- 9. All-atoms MD of HIV-1 CA tube • • • • • 71 hexamers 13 million atoms 10 ns MDFF coupled to density 125 ns MD, Blue waters NAMD Early Science System
- 10. NAMD Benchmarks on the Early Science System (no-GPU)
- 11. MDFF Structural Refinement hydrophobic interaction at trimeric a view into the trimeric interface, interface, surr. by polar residues contacts between three helices_10 formation of peripheral hydrogen bonds
- 12. Modeling of Pentameric Oligomers CA-Pentamer (1.3 M atoms) 1.5 µs simulation on Titan, GPU accelerated Pentamer-of-Hexamers (POH) P/H H10 H10 H10 H Hexamer-of-Hexamers (HOH) H Compare: (1) H10 superimposed from HOH, (2) H10 from POH; clearly pentamer H10 moves a lot, H10(P)+H10(H)^2 become more compact than H10(H)^3
- 13. MD:HIV-1 CA pentamer-hexamer • • • 1.3 million atoms 1.5 µs MD NAMD GPU-accelerated on NVIDIA Fermi GPU
- 14. CA CTD trimer interface A204 I201 E213 K203 100nm A204C 75 50 37 25 WT A204C CA6 WT A204C Core Associated CA (%) WT mature Infectivity (% of WT) A204C assembles efficiently into cones A204C cross-links only in mature virions Gongpu Zhao WT 204C Ernest Yufenyu & Chris Aiken 204D 204L 204K 204Y
- 15. Analogy with fullerenes High correlation with experimental density The parameter ξ measures the deviation of the fullerene from a perfect sphere and the strength of its deformation. A perfect sphere corresponds to ξ=0, and an axially symmetric ellipsoid corresponds to ξ=1. Fitted structure High strain region
- 16. Isomer search and geometry optimization Spiral search on 2D-projection 3D-embedding DFT geometry optimization
- 18. All-atom MD simulation of mature HIV-1 capsid • • • • 216 hexamers +12 pentamers (13.4 M), 64 million atoms total including solvent 100 ns running NAMD on 4000 Cray-XE nodes, 128000 cores 6 ns/day, all-atom
- 19. All-atom MD simulation of mature HIV-1 capsid • • • • 186 hexamers +12 pentamers (12 M), 64 million atoms total 100 ns running NAMD on NCSA Blue Waters 2000 to 3500 XK Nodes equipped with NVIDIA Tesla K20X 9 to 12 ns/day
- 20. PDB Molecule of the month Paper folding model www.pdb.org Courtesy of David Goodsell (Scripps)
- 21. Acknowledgments Peijun Zhang Angela M. Gronenborn Department of Structural Biology Center for HIV Protein Interactions University of Pittsburgh School of Medicine Christopher Aiken Department of Pathology, Microbiology and Immunology Vanderbilt University Medical Center
- 22. Acknowledgments John Stone VMD Jim Phillips NAMD Theoretical and Computational Biophysics Group University of Illinois Urbana-Champaign
- 23. Upcoming GTC Express Webinars July 25 - ACEMD: High-throughput Molecular Dynamics with NVIDIA Kepler GPUs July 30 - Getting Started with GPU-accelerated Computer Vision using OpenCV and CUDA July 31 - NMath Premium: GPU-accelerated Math Libraries for .NET Register at www.gputechconf.com/gtcexpress
- 24. GTC 2014 Call for Submissions Looking for submissions in the fields of Science and research Professional graphics Mobile computing Automotive applications Game development Cloud computing Submit at www.gputechconf.com
- 25. Test Drive K20 GPUs! Experience The Acceleration Questions? Contact us Run NAMD on Tesla K20 GPU today Devang Sachdev - NVIDIA dsachdev@nvidia.com @DevangSachdev Sign up for FREE GPU Test Drive on remotely hosted clusters www.nvidia.com/GPUTestDrive Dr. Juan R. Perilla – UIUC juan@ks.uiuc.edu www.ks.uiuc.edu Stream other webinars from GTC Express: www.gputechconf.com/gtcexpress