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An open-source drug discovery platform enables ultra-large virtual screens 期刊论文
NATURE, 2020, 580 (7805) : 663-+
作者:  Peron, Simon;  Pancholi, Ravi;  Voelcker, Bettina;  Wittenbach, Jason D.;  olafsdottir, H. Freyja;  Freeman, Jeremy;  Svoboda, Karel
收藏  |  浏览/下载:50/0  |  提交时间:2020/07/03

VirtualFlow, an open-source drug discovery platform, enables the efficient preparation and virtual screening of ultra-large ligand libraries to identify molecules that bind with high affinity to target proteins.


On average, an approved drug currently costs US$2-3 billion and takes more than 10 years to develop(1). In part, this is due to expensive and time-consuming wet-laboratory experiments, poor initial hit compounds and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening has the potential to mitigate these problems. With structure-based virtual screening, the quality of the hits improves with the number of compounds screened(2). However, despite the fact that large databases of compounds exist, the ability to carry out large-scale structure-based virtual screening on computer clusters in an accessible, efficient and flexible manner has remained difficult. Here we describe VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we prepared one of the largest and freely available ready-to-dock ligand libraries, with more than 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened more than 1 billion compounds and identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. One of the lead inhibitors (iKeap1) engages KEAP1 with nanomolar affinity (dissociation constant (K-d) = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and identify molecules that bind with high affinity to target proteins.


  
Control and single-shot readout of an ion embedded in a nanophotonic cavity 期刊论文
NATURE, 2020, 580 (7802) : 201-+
作者:  Rollie, Clare;  Chevallereau, Anne;  Watson, Bridget N. J.;  Chyou, Te-yuan;  Fradet, Olivier;  McLeod, Isobel;  Fineran, Peter C.;  Brown, Chris M.;  Gandon, Sylvain;  Westra, Edze R.
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Distributing entanglement over long distances using optical networks is an intriguing macroscopic quantum phenomenon with applications in quantum systems for advanced computing and secure communication(1,2). Building quantum networks requires scalable quantum light-matter interfaces(1) based on atoms(3), ions(4) or other optically addressable qubits. Solid-state emitters(5), such as quantum dots and defects in diamond or silicon carbide(6-10), have emerged as promising candidates for such interfaces. So far, it has not been possible to scale up these systems, motivating the development of alternative platforms. A central challenge is identifying emitters that exhibit coherent optical and spin transitions while coupled to photonic cavities that enhance the light-matter interaction and channel emission into optical fibres. Rare-earth ions in crystals are known to have highly coherent 4f-4f optical and spin transitions suited to quantum storage and transduction(11-15), but only recently have single rare-earth ions been isolated(16,17) and coupled to nanocavities(18,19). The crucial next steps towards using single rare-earth ions for quantum networks are realizing long spin coherence and single-shot readout in photonic resonators. Here we demonstrate spin initialization, coherent optical and spin manipulation, and high-fidelity single-shot optical readout of the hyperfine spin state of single Yb-171(3+) ions coupled to a nanophotonic cavity fabricated in an yttrium orthovanadate host crystal. These ions have optical and spin transitions that are first-order insensitive to magnetic field fluctuations, enabling optical linewidths of less than one megahertz and spin coherence times exceeding thirty milliseconds for cavity-coupled ions, even at temperatures greater than one kelvin. The cavity-enhanced optical emission rate facilitates efficient spin initialization and single-shot readout with conditional fidelity greater than 95 per cent. These results showcase a solid-state platform based on single coherent rare-earth ions for the future quantum internet.


Single ytterbium ion qubits in nanophotonic cavities have long coherence times and can be optically read out in a single shot, establishing them as excellent candidates for optical quantum networks.


  
Submicrosecond entangling gate between trapped ions via Rydberg interaction 期刊论文
NATURE, 2020, 580 (7803) : 345-+
作者:  Chatterjee, Sourav;  Guidi, Mara;  Seeberger, Peter H.;  Gilmore, Kerry
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

Generating quantum entanglement in large systems on timescales much shorter than the coherence time is key to powerful quantum simulation and computation. Trapped ions are among the most accurately controlled and best isolated quantum systems(1) with low-error entanglement gates operated within tens of microseconds using the vibrational motion of few-ion crystals(2,3). To exceed the level of complexity tractable by classical computers the main challenge is to realize fast entanglement operations in crystals made up of many ions (large ion crystals)(4). The strong dipole-dipole interactions in polar molecule(5) and Rydberg atom(6,7) systems allow much faster entangling gates, yet stable state-independent confinement comparable with trapped ions needs to be demonstrated in these systems(8). Here we combine the benefits of these approaches: we report a two-ion entangling gate with 700-nanosecond gate time that uses the strong dipolar interaction between trapped Rydberg ions, which we use to produce a Bell state with 78 per cent fidelity. The sources of gate error are identified and a total error of less than 0.2 per cent is predicted for experimentally achievable parameters. Furthermore, we predict that residual coupling to motional modes contributes an approximate gate error of 10(-4) in a large ion crystal of 100 ions. This provides a way to speed up and scale up trapped-ion quantum computers and simulators substantially.


  
Current-driven magnetic domain-wall logic 期刊论文
NATURE, 2020, 579 (7798) : 214-+
作者:  Culp, Elizabeth J.;  Waglechner, Nicholas;  Wang, Wenliang;  Fiebig-Comyn, Aline A.;  Hsu, Yen-Pang;  Koteva, Kalinka;  Sychantha, David;  Coombes, Brian K.;  Van Nieuwenhze, Michael S.;  Brun, Yves, V;  Wright, Gerard D.
收藏  |  浏览/下载:44/0  |  提交时间:2020/07/03

Spin-based logic architectures provide nonvolatile data retention, near-zero leakage, and scalability, extending the technology roadmap beyond complementary metal-oxide-semiconductor logic(1-13). Architectures based on magnetic domain walls take advantage of the fast motion, high density, non-volatility and flexible design of domain walls to process and store information(1,3,14-16). Such schemes, however, rely on domain-wall manipulation and clocking using an external magnetic field, which limits their implementation in dense, large-scale chips. Here we demonstrate a method for performing all-electric logic operations and cascading using domain-wall racetracks. We exploit the chiral coupling between neighbouring magnetic domains induced by the interfacial Dzyaloshinskii-Moriya interaction(17-20), which promotes non-collinear spin alignment, to realize a domain-wall inverter, the essential basic building block in all implementations of Boolean logic. We then fabricate reconfigurable NAND and NOR logic gates, and perform operations with current-induced domain-wall motion. Finally, we cascade several NAND gates to build XOR and full adder gates, demonstrating electrical control of magnetic data and device interconnection in logic circuits. Our work provides a viable platform for scalable all-electric magnetic logic, paving the way for memory-in-logic applications.


  
Variability of Intraseasonal Oscillations and Synoptic Signals in Sea Surface Salinity in the Bay of Bengal 期刊论文
JOURNAL OF CLIMATE, 2019, 32 (20) : 6703-6728
作者:  Trott, Corinne B.;  Subrahmanyam, Bulusu;  Roman-Stork, Heather L.;  Murty, V. S. N.;  Gnanaseelan, C.
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/27
Convection  Madden-Julian oscillation  Ocean dynamics  Atmosphere-ocean interaction  Synoptic-scale processes  
Tropical Synoptic-Scale Waves Propagating Across the Maritime Continent and Northern Australia 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2019, 124 (14) : 7665-7682
作者:  Fukutomi, Yoshiki
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
Asian-Australian monsoon  Maritime Continent  equatorial waves  tropical-extratropical interaction  tropical synoptic-scale waves  winter monsoon  
Modeling the Transient Response of Tropical Convection to Mesoscale SST Variations 期刊论文
JOURNAL OF THE ATMOSPHERIC SCIENCES, 2019, 76 (5) : 1227-1244
作者:  Skyllingstad, Eric D.;  39;Neill, Larry W.
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/26
Atmosphere-ocean interaction  Convective storms  systems  Convective-scale processes  Deep convection  Mesoscale processes  
The atmospheric responses to the intensity variability of subtropical front in the wintertime North Pacific 期刊论文
CLIMATE DYNAMICS, 2019, 52: 5623-5639
作者:  Wang, LiYing;  Hu, HaiBo;  Yang, XiuQun
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/26
North Pacific STFZ  Intensity variation  Synoptic-scale transient eddy  Midlatitude air-sea interaction  
Differences in Eddy-Correlation and Energy-Balance Surface Turbulent Heat Flux Measurements and Their Impacts on the Large-Scale Forcing Fields at the ARM SGP Site 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2019, 124 (6) : 3301-3318
作者:  Tang, Shuaiqi;  Xie, Shaocheng;  Zhang, Minghua;  Tang, Qi;  Zhang, Yunyan;  Klein, Stephen A.;  Cook, David R.;  Sullivan, Ryan C.
收藏  |  浏览/下载:18/0  |  提交时间:2019/11/26
eddy correlation  surface energy balance  large-scale forcing  land-atmosphere interaction  surface vegetation type  
Parameterization of Vertical Profiles of Governing Microphysical Parameters of Shallow Cumulus Cloud Ensembles Using LES with Bin Microphysics 期刊论文
JOURNAL OF THE ATMOSPHERIC SCIENCES, 2019, 76 (2) : 533-560
作者:  Khain, Pavel;  Heiblum, Reuven;  Blahak, Ulrich;  Levi, Yoav;  Muskatel, Harel;  Vadislavsky, Elyakom;  Altaratz, Orit;  Koren, Ilan;  Dagan, Guy;  Shpund, Jacob;  Khain, Alexander
收藏  |  浏览/下载:15/0  |  提交时间:2019/04/09
Cloud microphysics  Cloud parameterizations  Cloud resolving models  Large eddy simulations  Subgrid-scale processes  Aerosol-cloud interaction