David Calkins

Learn More
Generating the appropriate protonation states of drug-like molecules in solution is important for success in both ligand- and structure-based virtual screening. Screening collections of millions of compounds requires a method for determining tautomers and their energies that is sufficiently rapid, accurate, and comprehensive. To maximise enrichment, the(More)
Hypoosmolar solutions were recently shown to produce a reversible conduction block of rabbit vagus nerve and to potentiate local anesthetic agents. The object of the present study was to determine the ability of neural tissue to recover structurally and functionally following exposure to hypoosmotic solutions. Cervical vagus nerves of rabbits were bathed in(More)
Return of sensory nerve function in rat molars following cut or crush injury to the inferior alveolar nerve (IAN) was measured by observing the jaw opening reflex (JOR) response of the digastric muscle to electrical stimulation of individual molars or the gingiva. The IAN was injured from a lateral approach to the mandibular ramus at a site approximately 2(More)
With the continued rise of phenotypic- and genotypic-based screening projects, computational methods to analyze, process, and ultimately make predictions in this field take on growing importance. Here we show how automated machine learning workflows can produce models that are predictive of differential gene expression as a function of a compound structure(More)
The recent article "Evaluation of pK(a) Estimation Methods on 211 Druglike Compounds" ( Manchester, J.; et al. J. Chem Inf. Model. 2010, 50, 565-571 ) reports poor results for the program Epik. Here, we highlight likely sources for the poor performance and describe work done to improve the performance. Running Epik in the mode intended to calculate pK(a)(More)
Steady-state partitioning of morphine between blood and cerebrospinal fluid (CSF) was evaluated in pigtailed monkeys at three ages: 2-3 days, 1 month and 1 year. Protein binding of morphine to serum proteins was assessed by ultrafiltration. Newborns showed a higher CSF to plasma ratio than the 1-month- or 1-year-old monkeys (0.506 vs. 0.369 or 0.374,(More)
  • 1