Edward W. Lowe

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Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand(More)
Discoidin domain receptor (DDR) 1 and 2 are transmembrane receptors that belong to the family of receptor tyrosine kinases (RTK). Upon collagen binding, DDRs transduce cellular signaling involved in various cell functions, including cell adhesion, proliferation, differentiation, migration, and matrix homeostasis. Altered DDR function resulting from either(More)
Small angle X-ray scattering (SAXS) is used for low resolution structural characterization of proteins often in combination with other experimental techniques. After briefly reviewing the theory of SAXS we discuss computational methods based on 1) the Debye equation and 2) Spherical Harmonics to compute intensity profiles from a particular macromolecular(More)
Three initial fits of 1ubi in a 6.6Å resolution synthesized density map had backbone RMSDs to the correct placement of 2.7, 2.9 and 6.6 Å. They have been refined with a Powell optimizer [5] in 10 iterations using 6 directions, 3 rotations a, β with 0.15 radians and γ with 0.075 radians starting direction to cover the entire euler(More)
Quantitative structure activity relationship (QSAR) modeling using high-throughput screening (HTS) data is a powerful technique which enables the construction of predictive models. These models are utilized for the in silico screening of libraries of molecules for which experimental screening methods are both cost- and time-expensive. Machine learning(More)
With the rapidly increasing availability of High-Throughput Screening (HTS) data in the public domain, such as the PubChem database, methods for ligand-based computer-aided drug discovery (LB-CADD) have the potential to accelerate and reduce the cost of probe development and drug discovery efforts in academia. We assemble nine data sets from realistic HTS(More)
Positive allosteric modulation of the metabotropic glutamate receptor subtype 5 was studied by conducting a comparative molecular field analysis on 118 benzoxazepine derivatives. The model with the best predictive ability retained significant cross-validated correlation coefficients of q(2) = 0.58 (r(2) = 0.81) yielding a standard error of 0.20 in pEC(50)(More)
Here, we present a GPU-accelerated OpenCL implementation of a back-propagation artificial neural network for the creation of QSAR models for drug discovery and virtual high-throughput screening. A QSAR model for HSD achieved an enrichment of 5.9 and area under the curve of 0.83 on an independent data set which signifies sufficient predictive ability for(More)
Small angle X-ray scattering (SAXS) is an experimental technique used for structural characterization of macromolecules in solution. Here, we introduce BCL::SAXS--an algorithm designed to replicate SAXS profiles from rigid protein models at different levels of detail. We first show our derivation of BCL::SAXS and compare our results with the experimental(More)
Several machine learning techniques were evaluated for the prediction of logP. The algorithms used include artificial neural networks (ANN), support vector machines (SVM) with the extension for regression, and kappa nearest neighbor (k-NN). Molecules were described using optimized feature sets derived from a series of scalar, two- and three-dimensional(More)