Papers by Bradley Feuston
Analytical Biochemistry, Feb 1, 2003
Antagonists to the human metabotropic glutamate receptor subtype 5a(mGluR 5a) have been implicate... more Antagonists to the human metabotropic glutamate receptor subtype 5a(mGluR 5a) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and ParkinsonÕs disease. To discover novel antagonists to the mGluR 5a , a functional assay measuring agonist-induced intracellular calcium release was developed. The assay was used for the high-throughput screening of a large collection of compounds in single wells using a fully automated robotic platform. Primary high-throughput screening hits were subjected to a combination of data analysis and counterscreening assays to identify several compounds with both efficacy and selectivity for the metabotropic glutamate receptor target.
Fragmentation and Structure of Silicon Microclysters
Springer eBooks, 1987
In the past several years there has been growing interest in the properties of small clusters of ... more In the past several years there has been growing interest in the properties of small clusters of atoms.1–7 Inert gas clusters are known to form predominantly 13-, 55-, etc. atom clusters explained by stable icosahedral packing.7 More recently there has been an effort to determine the geometrical arrangements and electronic configurations for Group IV elements, C, Si, Ge and Sn.8–11 Silicon and germanium have both been found to form unusually stable 6- and 10-atom clusters. Si4 and Ge14 are also found to be particularly stable. These unusually stable clusters are referred to as the magic numbers. Unlike Si and Ge, carbon exhibits chain-like structures due to strong π bonding with their own set of magic numbers. Bloomfield, Freeman, and Brown8 (BFB) performed a photofragmentation experiment on ionized silicon, measuring relative cross sections and individual fragmentation channels for clusters containing upto 12 atoms. Neutral clusters were created by vaporizing bulk silicon in the presence of a stream of inert gas. These clusters were then ionized by a laser and mass selected by means of electrodes. Fragmentation occurred upon exposing the cluster to an intense beam of laser radiation. The size of the resulting charged fragment was then determined. The temperature of the cluster prior to dissociation reaches the order of the melting temperature of bulk silicon (T ~ 2000 K). The fragmentation channels were found to depend critically on the overlap between the laser beam and the cluster. Bloomfield et al. report relatively low total photofragmentation cross sections for Si+ 4, Si+ 6, and Si+ 10 in addition to the unusually common occurrence of Si+ 6 and Si+ 10 from the fragmentation of Si+ 7−11 and Si+ 12, respectively. The magic numbers for silicon have been determined to be 4, 6, and 10 from these experimental results.
Biophysical Journal, 2014
Nonpeptide α<sub>v</sub>β<sub>3</sub> Antagonists. Part 11: Discovery and Preclinical Evaluation of Potent α<sub>v</sub>β<sub>3</sub> Antagonists for the Prevention and Treatment of Osteoporosis
Journal of Medicinal Chemistry, Aug 26, 2004
3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(... more 3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.
Application of a New Three-Body Potential to Vitreous Silica and Sodium Silicate Glasses
MRS Proceedings, 1988
An empirical three-body potential, suitable for molecular dynamics (MD) simulations, has been dev... more An empirical three-body potential, suitable for molecular dynamics (MD) simulations, has been developed to model the natural covalency of the Si-O bond in vitreous silica and silicate glass systems. Through the addition of a small directional-dependent three-body term to a previously used modified ionic pair interaction, a narrow distribution of tetrahedral angles and a low concentration of defects were obtained, in good agreement with experiment. The structure of bulk silica resulting from the MD technique also contained a larger average ring size, no edge-sharing tetrahedra, and a calculated static structure factor in good agreement with neutron diffraction results. The simulated sodium silicate glass was also largely improved over previous simulations using pair interactions alone. All silicon atoms were found to be exactly four coordinated while the number of non-bridging oxygen nearly equaled the number of sodium ions present with a reasonable distribution of Qi species.
Quantum Molecular Dynamics with Gaussian Basis Set
Modem Techniques in Computational Chemistry: MOTECC-91, 1991
Journal of Chemical Information and Modeling, 2005
Journal of Chemical Information and Computer Sciences, 2003
A new classification and regression tool, Random Forest, is introduced and investigated for predi... more A new classification and regression tool, Random Forest, is introduced and investigated for predicting a compound's quantitative or categorical biological activity based on a quantitative description of the compound's molecular structure. Random Forest is an ensemble of unpruned classification or regression trees created by using bootstrap samples of the training data and random feature selection in tree induction. Prediction is made by aggregating (majority vote or averaging) the predictions of the ensemble. We built predictive models for six cheminformatics data sets. Our analysis demonstrates that Random Forest is a powerful tool capable of delivering performance that is among the most accurate methods to date. We also present three additional features of Random Forest: built-in performance assessment, a measure of relative importance of descriptors, and a measure of compound similarity that is weighted by the relative importance of descriptors. It is the combination of relatively high prediction accuracy and its collection of desired features that makes Random Forest uniquely suited for modeling in cheminformatics.
Generalized nonlinear regression with ensemble of neural nets: The great energy predictor shootout
A novel approach to data modeling has been developed using an ensemble of artificial neural netwo... more A novel approach to data modeling has been developed using an ensemble of artificial neural networks. This development has been driven by the need in the petroleum business to model data that has poorly defined independent ,parameters, poor repeatability and/or reproducibility (more than {+-}10% variation in repeated measurements), and relatively few data sets. Their objective for entering ``The Great Energy Predictor Shootout`` was to evaluate the efficiency of their approach. In particular, the authors were interested in how quickly a model could be constructed and the accuracy of the model`s predictions. This scientific competition was ostensibly organized to compare various modeling methodologies applied to both time-dependent (dynamic) and time-independent problems. Both problems were given to the participants with little descriptive information. The objective of this competition was to train (or fit) a model given a complete set of data (independent and dependent variables) and then blindly predict the dependent variables when given only the independent variables of a different data set. The predictions were then sent to the organizers for evaluation. While their entry ranked third overall, the models were generated with less than one man-day of effort -- far less than the two months required by the first-place winnermore » and the one to one-and-one-half months spent by the other winners.« less
Model Structures for MCM-41 Materials: A Molecular Dynamics Simulation
The Journal of Physical Chemistry, 1994
... This ratio of intensities is much greater than 1.0 for the thin wall models, approximately eq... more ... This ratio of intensities is much greater than 1.0 for the thin wall models, approximately equal to 1 .O for the structures with walls around 8 A thick, and much less than 1 .O for the walls greater 1 1 A. The latter is a signature of the observed X-ray diffraction pattern for all MCM-41 ...
Model Structures for MCM-41 Materials: A Molecular Dynamics Simulation
The Journal of Physical Chemistry, 1994
... This ratio of intensities is much greater than 1.0 for the thin wall models, approximately eq... more ... This ratio of intensities is much greater than 1.0 for the thin wall models, approximately equal to 1 .O for the structures with walls around 8 A thick, and much less than 1 .O for the walls greater 1 1 A. The latter is a signature of the observed X-ray diffraction pattern for all MCM-41 ...
Book Review. Review of Modelling of Structure and Reactivity in Zeolite, by C. R. A. Catlow
Journal of Solid State Chemistry, 1993
Selected topics in ab initio computational chemistry in both very small and very large chemical systems
Chemical Reviews, 1991
Selected Topics In ab Initio Computational Chemistry in Both Very Small and ... ENRICO CLEMENTI.&... more Selected Topics In ab Initio Computational Chemistry in Both Very Small and ... ENRICO CLEMENTI.&amp;amp;#x27; GIORGINA CORONGIU. DELEEP BAHAlTACHARYA, BRADLEY FEUSTON. DANIEL FRY, ALEXANDRA PREISKORN. ANTONIO RIZZO.&amp;amp;#x27; and WElGE XU
Molecular Umbrella Conjugate for the Ocular Delivery of siRNA
Bioconjugate Chemistry, 2014
The synthesis, computer modeling, and biological activity of an octawalled molecular umbrella sho... more The synthesis, computer modeling, and biological activity of an octawalled molecular umbrella short interfacing RNA (siRNA) conjugate is described. This molecular umbrella-siRNA conjugate exhibited mRNA knockdown activity in vitro in the absence of a transfection reagent. Evaluation of this molecular umbrella conjugate in vivo, using the rat eye via intravitreal injection, resulted in sequence specific mRNA knockdown in the retina with no obvious signs of toxicity, as judged by ophthalmic examination.
Molecular Model of the a IIb � 3 Integrin
J Med Chem, 2003
Classical and quantum simulations via molecular dynamics /
Thesis (Ph. D.)--University of Cincinnati, 1987. Includes bibliographical references. Includes ab... more Thesis (Ph. D.)--University of Cincinnati, 1987. Includes bibliographical references. Includes abstract.
Targeted purification development enabled by computational biophysical modeling
Biotechnology progress, 2015
Chromatographic and non-chromatographic purification of biopharmaceuticals depend on the interact... more Chromatographic and non-chromatographic purification of biopharmaceuticals depend on the interactions between protein molecules and a solid-liquid interface. These interactions are dominated by the protein-surface properties, which are a function of protein sequence, structure, and dynamics. In addition, protein-surface properties are critical for in vivo recognition and activation, thus, purification strategies should strive to preserve structural integrity and retain desired pharmacological efficacy. Other factors such as surface diffusion, pore diffusion, and film mass transfer can impact chromatographic separation and resin design. The key factors that impact non-chromatographic separations (e.g., solubility, ligand affinity, charges and hydrophobic clusters, and molecular dynamics) are readily amenable to computational modeling and can enhance the understanding of protein chromatographic. Previously published studies have used computational methods such as quantitative structur...
Molecular-orientational pinning on a surface: A simulated annealing study
Physical review. A, 1988
Orientational properties of a quantum rotor interacting with a classical substrate are investigat... more Orientational properties of a quantum rotor interacting with a classical substrate are investigated by dynamical simulated annealing. At zero temperature a transition in the molecular orientation is observed when the molecule-substrate coupling exceeds a critical value ..cap alpha../sub c/. For very light molecules we find a smooth transition and a decrease in ..cap alpha../sub c/ with an increase in the
Electronic and vibrational properties of C60 at finite temperature from ab initio molecular dynamics
Physical Review B, 1991
A Car-Parrinello molecular-dynamics study of C60 in the fullerene structure has been performed. T... more A Car-Parrinello molecular-dynamics study of C60 in the fullerene structure has been performed. The ground-state properties were calculated and found to be in agreement with other theoretical estimates. The finite-temperature properties of such clusters are computed. These can be directly compared to experiments performed at finite temperature. The comparison is very favorable for structural, vibrational, and electronic properties.
Virtual Fragment Scanning: Current Trends, Applications and Web-Based Tools
Fragment-Based Drug Discovery, 2008
9 Virtual Fragment Scanning: Current Trends, Applications and Web-based Tools Bradley Feuston, M.... more 9 Virtual Fragment Scanning: Current Trends, Applications and Web-based Tools Bradley Feuston, M. Katharine Holloway, Georgia McGaughey and J. Christopher Culberson 9.1 Introduction Significantresourcesare currentlydevotedtoscreeningfragmentdatabases withthegoalof ...
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Papers by Bradley Feuston