A5083358022- Lipid Membrane Structure and Behavior
- Spectroscopy and Quantum Chemical Studies
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Analytical Chemistry and Chromatography
- Molecular spectroscopy and chirality
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- DNA and Nucleic Acid Chemistry
- Various Chemistry Research Topics
- Metabolomics and Mass Spectrometry Studies
- Estrogen and related hormone effects
- Genetics, Bioinformatics, and Biomedical Research
- Surfactants and Colloidal Systems
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Advanced NMR Techniques and Applications
- Advanced Statistical Methods and Models
- Thermodynamic properties of mixtures
- Nitric Oxide and Endothelin Effects
- Chemistry and Chemical Engineering
- Free Radicals and Antioxidants
- Bioinformatics and Genomic Networks
- Advanced Chemical Sensor Technologies
Bristol-Myers Squibb (United States)
1995-2020
Integral Consulting (United States)
2020
Lawrence Livermore National Laboratory
2018
Institute for Computer Aided Design
2010-2015
Innovimmune Biotherapeutics (United States)
2015
Lexicon Pharmaceuticals (United States)
2007-2014
Science Education Solutions (United States)
2012
Princeton University
2011
Bristol-Myers Squibb (Germany)
1992-2009
Windsor Dermatology
2009
To elucidate the mechanism of solute diffusion through lipid bilayer membranes, nearly 4 ns molecular dynamics simulations solutes in phospholipid bilayers was conducted. The study, first atomic level study a bilayer, involved four an all-atom representation fully solvated dimyristoylphosphatidylcholine (DMPC) L alpha phase with benzene molecules as solutes, totaling over 7100 atoms. These agree experimental evidence that presence small does not affect thickness but result slight...
The human intestinal oligopeptide transporter (PEPT1) facilitates the absorption of dipeptides, tripeptides, and many peptidomimetic drugs. In this study, a large number peptides were selected to investigate structural features required for PEPT1 transport. Binding affinity was determined in Gly-Sar uptake inhibition assay, whereas functional transport ranked membrane depolarization assay. Although most tested could bind PEPT1, not all substrates. As expected, single amino acids...
We report molecular dynamics simulations of water hydrating a lipid (dimyristoylphosphatidylcholine) monolayer under conditions chosen to eliminate simulation artifacts. These provide description the behavior membrane–water interface that agrees with recent experimental studies. In particular, we find orients contribute positive end its dipole substantially electrostatic potential membrane interior, consistent interpretations experiments. addition, experiments show this reorients rapidly on...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA simple method for the representation, quantification, and comparison of volumes shapes chemical compoundsTerry R. Stouch Peter C. JursCite this: J. Chem. Inf. Comput. Sci. 1986, 26, 1, 4–12Publication Date (Print):February 1986Publication History Published online1 May 2002Published inissue 1 February 1986https://pubs.acs.org/doi/10.1021/ci00049a002https://doi.org/10.1021/ci00049a002research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of Solute Diffusion through Lipid Bilayer Membranes by Molecular Dynamics SimulationDonna Bassolino-Klimas, Howard E. Alper, and Terry R. StouchCite this: J. Am. Chem. Soc. 1995, 117, 14, 4118–4129Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ja00119a028https://doi.org/10.1021/ja00119a028research-articleACS PublicationsRequest reuse...
Molecular dynamics simulations of water above a lipid (dimyristoylphosphatidylcholine) monolayer show that the structure and are quite sensitive to treatment long range forces. To obtain quantitative estimate perturbations introduced into behavior by truncation potential, we calculate various structural dynamical properties for employing different cutoffs. When potential cutoffs on order 10–14 Å employed, near exhibit up 20%–25% extend 30–35 water. Employing 30 leads is essentially uniform...
Abstract The structure and dynamics of phosphatidylcholine bilayers are examined by reviewing the results several nanoseconds molecular simulations on a number bilayer monolayer models. lengths these simulations, longest single one which was 2 nanoseconds, were sufficiently long to effectively sample many longer-scale motions governing behaviour biomembranes. These reproduce experimental observables well provide degree resolution currently unavailable experimentally.
The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment ocular hypertension associated glaucoma, is disclosed. Previously reported LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis central urea. Replacement urea with hindered amide resulted in stable compounds, addition solubilizing groups set compounds good properties topical dosing eye efficacy mouse model hypertension. LX7101 was selected as clinical candidate this group based on superior...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of Switching Functions on the Behavior Liquid Water in Molecular Dynamics SimulationsKit Fun Lau, Howard E. Alper, Thomas S. Thacher, and Terry R. StouchCite this: J. Phys. Chem. 1994, 98, 35, 8785–8792Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/j100086a032https://doi.org/10.1021/j100086a032research-articleACS PublicationsRequest...
Abstract Atomic monopoles are routinely determined through a least squares fit to molecular electrostatic potentials. We report studies of the variation in atomic with conformation for zwitterionic polar head group lecithins, common class lipid. The monopole one atom, relatively buried carbon, varied by 1.3 electron units between different conformers. “Exterior” atoms, as seen previously, showed smaller changes charge and estimated standard deviations. total local groups atoms less than...
The discovery of a novel class peripheral tryptophan hydroxylase (TPH) inhibitors is described. This TPH exhibits excellent potency in vitro biochemical and cell-based assays, it selectively reduces serotonin levels the murine intestine after oral administration without affecting brain. These TPH1 may provide treatments for gastrointestinal disorders associated with dysregulation serotonergic system, such as chemotherapy-induced emesis irritable bowel syndrome.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrientation and Diffusion of a Drug Analog in Biomembranes: Molecular Dynamics SimulationsHoward E. Alper Terry R. StouchCite this: J. Phys. Chem. 1995, 99, 15, 5724–5731Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/j100015a065https://doi.org/10.1021/j100015a065research-articleACS PublicationsRequest reuse permissionsArticle...
Abstract Atomic monopole “point charges” are routinely determined through a least squares fit to molecular electrostatic potentials [potential‐derived (PD) charges]. Previously, it has been shown that these charges vary with variation in conformation. Also, observed swings highly correlated between neighboring atoms. Here, we examine the variance–covariance data matrices for set of literature and find further indications high colinearity within data. These colinearities effectively reduce...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAb initio studies of lipid model species. 1. Dimethyl phosphate and methyl propyl anionsCongxin Liang, Carl S. Ewig, Terry R. Stouch, Arnold T. HaglerCite this: J. Am. Chem. Soc. 1993, 115, 4, 1537–1545Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/ja00057a046https://doi.org/10.1021/ja00057a046research-articleACS PublicationsRequest reuse...
On the basis of stucture genistein, a new series 3-arylquinazolines was prepared and tested for their estrogen receptor (ER) α β affinities. 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4(3H)-quinazolinone (1aa) acts as an agonist on both ER subtypes. It has 62-fold higher binding affinity [IC50(ERβ) = 179 nM] 38-fold functional potency in transcription assay [EC50(ERβ) 76 with ERβ than ERα, thus improving upon selectivity genistein. All analogues showed preferential ERβ. Many are also more potent...
Abstract We evaluate an empirical potential energy function and associated parameters for classical molecular dynamics simulations of lecithins, a common class lipid. The physical accuracy the force field was tested through its application to known crystal structures lipid molecules. Average atomic positions conformation are well maintained during despite considerable thermal motion. Calculated isotropic temperature factors correlate highly with those from experiment.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputer-assisted studies of molecular structure biological activity relationshipsPeter C. Jurs, Terry R. Stouch, Maria Czerwinski, and Javier N. NarvaezCite this: J. Chem. Inf. Comput. Sci. 1985, 25, 3, 296–308Publication Date (Print):August 1, 1985Publication History Published online1 May 2002Published inissue 1 August 1985https://pubs.acs.org/doi/10.1021/ci00047a028https://doi.org/10.1021/ci00047a028research-articleACS PublicationsRequest reuse...