13 research outputs found

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

    Zero Thermal Expansion in ZrMgMo<sub>3</sub>O<sub>12</sub>: NMR Crystallography Reveals Origins of Thermoelastic Properties

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    The coefficient of thermal expansion of ZrMgMo<sub>3</sub>O<sub>12</sub> has been measured and was found to be extremely close to zero over a wide temperature range including room temperature (αl = (1.6 ± 0.2) × 10<sup>–7</sup> K<sup>–1</sup> from 25 to 450 °C by X-ray diffraction (XRD)). ZrMgMo<sub>3</sub>O<sub>12</sub> belongs to the family of AMgM<sub>3</sub>O<sub>12</sub> materials, for which coefficients of thermal expansion have previously been reported to range from low-positive to low-negative. However, the low thermal expansion property had not previously been explained because atomic position information was not available for any members of this family of materials. We determined the structure of ZrMgMo<sub>3</sub>O<sub>12</sub> by nuclear magnetic resonance (NMR) crystallography, using <sup>91</sup>Zr, <sup>25</sup>Mg, <sup>95</sup>Mo, and <sup>17</sup>O magic angle spinning (MAS) and <sup>17</sup>O multiple quantum MAS (MQMAS) NMR in conjunction with XRD and density functional theory calculations. The resulting structure was of sufficient detail that the observed zero thermal expansion could be explained using quantitative measures of the properties of the coordination polyhedra. We also found that ZrMgMo<sub>3</sub>O<sub>12</sub> shows significant ionic conductivity, a property that is also related to its structure
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