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

: 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

Three Studies of the Effectiveness of Sulfonylurea Herbicides Applied to Nutsedge and Broadleaf Weed Species in Dark Fired Tobacco Production

In the Donoho, Tilford, Hooks and Bowman study, the effectiveness of two different herbicide applications that are not currently labeled for tobacco were evaluated. Two separate experiments were conducted to evaluate the potential for the use of two sulfonylurea herbicides, CGA362622 (Trifoxysulfurson-sodium) and halosulfuron-methyl, in dark tobacco. Currently sulfonylurea herbicides are applied post emergence over-the-top in corn and soybeans to control broadleaf weeds. Sulfonylurea herbicides controls a wide variety of weeds at low rates, exhibit crop/weed selectivity, have low environmental persistence, and low mammalian toxicity. Each herbicide was applied either post emergence over-the-top on month after setting or post emergence directed eight weeks after planting. Herbicides were planted at rates of 0.07 or 0.10 oz/A for trifloxysulfuron and 0.07 or 1.0 oz/A for halosulfuron-methyl. Applications were made with a CO2-pressurized backpack plot sprayer calibrated to deliver twenty gallons per acre with flat fan spray nozzles. Over-the-top applications were made with a 4-nozzle spray boom with twenty-inch spacing. In the Moss, Rogers, Hayden, and Morgan study, replicated trials were conducted to compare the advantages and disadvantages of current commercial dark tobacco varieties during the 2004 season. Varieties tested include DF 911, DT 538, DT 518, KY 171, TN D950, VA 359, VA 309, Little Crittenden, TR Madole, and Narrow-leaf Madole. SN 2108 is a black shank resistant variety tested that will be available in the market next year. The layout of the test plots was a randomized complete block design with four replications. The following herbicides were applied: 1.1 pounds of pendimethalin per acre and 4 ounces of sulfentrazone per acre. The plots were transplanted in the field on June 9, 2004 and no irrigation was applied. Plants were detopped on July 28, 2004. Suckers were controlled by applying a butralin and fatty alcohol mix to each plant. The plants were harvested between the dates of September 20th through 22nd. The overall yields, yield of each leaf grade, and the quality of the leaves from each variety will be reported. Statistical analyses will be conducted to determine differences between the varieties. Hall, Swiney, and Williams hoped to better enable dark-fired tobacco producers to select the best varieties of tobacco. They conducted replicated trials to compare the advantages and disadvantages of current commercial dark tobacco varieties during the 2003 season. The layout of the test plots was a randomized complete block design with four replications. Each plot was 300 ft2, with 4,900 plants per acre. The amount of fertilizer applied was 300 lbs N, 30 lbs P2O5, and 80 lbs of K2O per acre, respectively. Post emergent herbicides used were Prowl at a rate of 1 and 1/3 qt/acre and Spartan (liquid form) at a rate of 12 oz/acre. The plots were transplanted into the field on June 9th. On August 4-7 the plants were detopped. Applying Butralin and a fatty alcohol mix to each plant controlled suckers. Plants were harvested, or housed in the barn on September 15-19. We will be reporting the overall yields, yield of each leaf grade, and the overall average income per acre of each variety. Statistical analyses were conducted to determine differences between the varieties