Taehoon Kim

CHARMM is an academic research program used widely for macromolecular mechanics and dynamics with versatile analysis and manipulation tools of atomic coordinates and dynamics trajectories. CHARMM-GUI, http://www.charmm-gui.org, has been developed to provide a web-based graphical user interface to generate various input files and molecular systems to facilitate and standardize the usage of common and advanced simulation techniques in CHARMM. The web environment provides an ideal platform to build and validate a molecular model system in an interactive fashion such that, if a problem is found through visual inspection, one can go back to the previous setup and regenerate the whole system again. In this article, we describe the currently available functional modules of CHARMM-GUI Input Generator that form a basis for the advanced simulation techniques. Future directions of the CHARMM-GUI development project are also discussed briefly together with other features in the CHARMM-GUI website, such as Archive and Movie Gallery.

Molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to solvation of globular proteins, building a realistic protein/membrane complex is still challenging and requires considerable experience with simulation software. Membrane Builder in the CHARMM-GUI website (http://www.charmm-gui.org) helps users to build such a complex system using a web browser with a graphical user interface. Through a generalized and automated building process including system size determination as well as generation of lipid bilayer, pore water, bulk water, and ions, a realistic membrane system with virtually any kinds and shapes of membrane proteins can be generated in 5 minutes to 2 hours depending on the system size. Default values that were elaborated and tested extensively are given in each step to provide reasonable options and starting points for both non-expert and expert users. The efficacy of Membrane Builder is illustrated by its applications to 12 transmembrane and 3 interfacial membrane proteins, whose fully equilibrated systems with three different types of lipid molecules (DMPC, DPPC, and POPC) and two types of system shapes (rectangular and hexagonal) are freely available on the CHARMM-GUI website. One of the most significant advantages of using the web environment is that, if a problem is found, users can go back and re-generate the whole system again before quitting the browser. Therefore, Membrane Builder provides the intuitive and easy way to build and simulate the biologically important membrane system.

CHARMM36 (C36) is the most up-to-date pairwise additive all-atom lipid force field and is able to accurately represent bilayer properties of saturated and monounsaturated lipid molecules in the natural constant particle, pressure, and temperature (NPT) ensemble. However, molecular dynamics (MD) simulations on 1-stearoyl-2-docosahexaenoyl-sn-glycerco-3-phosphocholine (SDPC) bilayers of the polyunsaturated fatty acid (PUFA) chains result in inaccuracies of the surface area per lipid (SA), deuterium order parameters (S(CD)), and X-ray form factors. Therefore, in this study, high-level quantum mechanical calculations are used to improve the dihedral potential of neighboring double bonds, and the corresponding force field is referred to as C36p. The SA for SDPC at 303 K increases from 63.2 ± 0.2 (C36) to 70.8 ± 0.2 (C36p) Å(2) and agrees favorably with X-ray diffraction results at 297 K. The resulting S(CD) are in excellent agreement with experimental values of both the sn-1 and sn-2 chains. Calculated NMR (13)C relaxation times and X-ray form factors from MD simulations of SDPC bilayers also agree with experiments. MD simulations of 1,2-diarachidonyl-phosphatidylcholine (DAPC) bilayers are used to further validate our force field parameters on a lipid with both chains containing PUFAs. As expected, the thickness of DAPC bilayers is reduced, and the SA is increased compared to the SDPC bilayers. This update in the PUFA force field should allow for accurate MD simulations of PUFA-containing bilayers in the NPT ensemble.

Traditional CPUs and cloud systems based on them have embraced the hardware-based trusted execution environments to securely isolate computation from malicious OS or hardware attacks. However, GPUs and their cloud deployments have yet to include such support for hardware-based trusted computing. As large amounts of sensitive data are offloaded to GPU acceleration in cloud environments, ensuring the security of the data is a current and pressing need. As deployed today, the outsourced GPU model is vulnerable to attacks from compromised privileged software. To support isolated remote execution on GPUs even under vulnerable operating systems, this paper proposes a novel hardware and software architecture, called HIX (Heterogeneous Isolated eXecution). HIX does not require modifications to the GPU architecture to offer protections: Instead, it offers security by modifying the I/O interconnect between the CPU and GPU, and by refactoring the GPU device driver to work from within the CPU trusted environment. A result of the architectural choices behind HIX is that the concept can be applied to other offload accelerators besides GPUs. This work implements the proposed HIX architecture on an emulated machine with KVM and QEMU. Experimental results from the emulated security support with a real GPU show that the performance overhead for security is curtailed to 26% on average for the Rodinia benchmark, while providing secure isolated GPU computing.