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Proton NRM spectroscopy of the active site histidine of α-lytic proteinase

William M. Westler, John L. Markley, William W. Bachovchin
1982 FEBS Letters  
M. and GM 27927 to W. W. B.  ...  Experimental conditions: protein was 2 mM in 2H20 containing 0.2 M KC1; probe temp. 25°C; pulse sequence, standard 90* pulse (10 ~s) followed by an aquisition time 0.819 s and a delay of 3 s; number of  ... 
doi:10.1016/0014-5793(82)80449-3 pmid:7040114 fatcat:wkxspvljjbccblxiqgvumsgqn4

1H NMR of intact muscle at 11 T

Carlos Arús, Michael Bárány, William M. Westler, John L. Markley
1984 FEBS Letters  
We thank Donna M. Lattyak for typing the manuscript.  ...  The soluble protein fraction was freeze-dried, and dissolved in 0.15 M NaCl containing 'H20.  ...  Myofibrils, mitochondria, and microsomes were suspended in 0.15 M NaCl, dissolved in 'HzO, for 'H NMR analysis.  ... 
doi:10.1016/0014-5793(84)80175-1 pmid:6607178 fatcat:kaeik23bozadzbc23gcly7hulm

Automated evaluation of consistency within the PubChem Compound database

Hesam Dashti, Jonathan R. Wedell, William M. Westler, John L. Markley, Hamid R. Eghbalnia
2019 Scientific Data  
Identification of discrepant data in aggregated databases is a key step in data curation and remediation. We have applied the ALATIS approach, which is based on the international chemical shift identifier (InChI) model, to the full PubChem Compound database to generate unique and reproducible compound and atom identifiers for all entries for which three-dimensional structures were available. This exercise also served to identify entries with discrepancies between structures and chemical
more » ... or InChI strings. The use of unique compound identifiers and atom nomenclature should support more rigorous links between small-molecule databases including those containing atom-specific information of the type available from crystallography and spectroscopy. The comprehensive results from this analysis are publicly available through our webserver [].
doi:10.1038/sdata.2019.23 pmid:30778259 pmcid:PMC6380220 fatcat:3gysuhgzsbbwdlq2jp6s3nlb3y

Ligand Binding and Substrate Discrimination by UDP-Galactopyranose Mutase

Todd D. Gruber, M. Jack Borrok, William M. Westler, Katrina T. Forest, Laura L. Kiessling
2009 Journal of Molecular Biology  
Lysate was cleared by centrifugation (15,000g) and filtration (0.2 μM).  ...  UGM (40 μM active sites), 4 mM ligand (UDP-Galp or UDP-Glc), and 10 μM deuterated 2,2-dimethyl-2-silapentane-5-sulfonic acid in 50 mM K 2 HPO 4 /KH 2 PO 4 (pH 7.6) in 99% D 2 O.  ... 
doi:10.1016/j.jmb.2009.05.081 pmid:19500588 pmcid:PMC2771219 fatcat:cb2f5aiywnbczlur6hdk27l7im

Unique identifiers for small molecules enable rigorous labeling of their atoms

Hesam Dashti, William M. Westler, John L. Markley, Hamid R. Eghbalnia
2017 Scientific Data  
Rigorous characterization of small organic molecules in terms of their structural and biological properties is vital to biomedical research. The three-dimensional structure of a molecule, its 'photo ID', is inefficient for searching and matching tasks. Instead, identifiers play a key role in accessing compound data. Unique and reproducible molecule and atom identifiers are required to ensure the correct cross-referencing of properties associated with compounds archived in databases. The best
more » ... roach to this requirement is the International Chemical Identifier (InChI). However, the current implementation of InChI fails to provide a complete standard for atom nomenclature, and incorrect use of the InChI standard has resulted in the proliferation of non-unique identifiers. We propose a methodology and associated software tools, named ALATIS, that overcomes these shortcomings. ALATIS is an adaptation of InChI, which operates fully within the InChI convention to provide unique and reproducible molecule and all atom identifiers. ALATIS includes an InChI extension for unique atom labeling of symmetric molecules. ALATIS forms the basis for improving reproducibility and unifying cross-referencing across databases.
doi:10.1038/sdata.2017.73 pmid:28534867 pmcid:PMC5441290 fatcat:p7gazcm73fdlxgqcsdfhurg7qe

NMRbot: Python scripts enable high-throughput data collection on current Bruker BioSpin NMR spectrometers

Lawrence J. Clos, M. Fransisca Jofre, James J. Ellinger, William M. Westler, John L. Markley
2013 Metabolomics  
To facilitate the high-throughput acquisition of nuclear magnetic resonance (NMR) experimental data on large sets of samples, we have developed a simple and straightforward automated methodology that capitalizes on recent advances in Bruker BioSpin NMR spectrometer hardware and software. Given the daunting challenge for non-NMR experts to collect quality spectra, our goal was to increase user accessibility, provide customized functionality, and improve the consistency and reliability of
more » ... t data. This methodology, NMRbot, is encoded in a set of scripts written in the Python programming language accessible within the Bruker BioSpin TopSpin TM software. NMRbot improves automated data acquisition and offers novel tools for use in optimizing experimental parameters on the fly. This automated procedure has been successfully implemented for investigations in metabolomics, smallmolecule library profiling, and protein-ligand titrations on four Bruker BioSpin NMR spectrometers at the National Magnetic Resonance Facility at Madison. The investigators reported benefits from ease of setup, improved spectral quality, convenient customizations, and overall time savings.
doi:10.1007/s11306-012-0490-9 pmid:23678341 pmcid:PMC3651530 fatcat:4i3o3yjn4vcptfilavozbagbbq

The Complex Energy Landscape of the Protein IscU

Jameson R. Bothe, Marco Tonelli, Ibrahim K. Ali, Ziqi Dai, Ronnie O. Frederick, William M. Westler, John L. Markley
2015 Biophysical Journal  
IscU, the scaffold protein for iron-sulfur (Fe-S) cluster biosynthesis in Escherichia coli, traverses a complex energy landscape during Fe-S cluster synthesis and transfer. Our previous studies showed that IscU populates two interconverting conformational states: one structured (S) and one largely disordered (D). Both states appear to be functionally important because proteins involved in the assembly or transfer of Fe-S clusters have been shown to interact preferentially with either the S or D
more » ... state of IscU. To characterize the complex structure-energy landscape of IscU, we employed NMR spectroscopy, small-angle x-ray scattering (SAXS), and differential scanning calorimetry. Results obtained for IscU at pH 8.0 show that its S state is maximally populated at 25 C and that heating or cooling converts the protein toward the D state. Results from NMR and DSC indicate that both the heat-and cold-induced S/D transitions are cooperative and two-state. Low-resolution structural information from NMR and SAXS suggests that the structures of the cold-induced and heat-induced D states are similar. Both states exhibit similar 1 H-15 N HSQC spectra and the same pattern of peptidyl-prolyl peptide bond configurations by NMR, and both appear to be similarly expanded compared with the S state based on analysis of SAXS data. Whereas in other proteins the cold-denatured states have been found to be slightly more compact than the heat-denatured states, these two states occupy similar volumes in IscU.
doi:10.1016/j.bpj.2015.07.045 pmid:26331259 pmcid:PMC4564936 fatcat:b44p57cgjzexre7qd2kcvsjtfe

Robust nomenclature and software for enhanced reproducibility in molecular modeling of small molecules [article]

Hesam Dashti, Jonathan R. Wedell, Gabriel Cornilescu, Charles D. Schwieters, William M. Westler, John L. Markley, Hamid R. Eghbalnia
2018 bioRxiv   pre-print
AbstractComputational molecular dynamics, energy minimization, and modeling of molecular interactions are widely used in studies involving natural products, metabolites, and drugs. Manually directed computational steps commonly utilize an evolving collection of experimental and computational data, to which new data sources are added or modified as needed. Several software packages capable of incorporating sources of data are available, but the process remains error prone owing to the
more » ... s of preparing and maintaining a consistent set of input files and the proper post-processing of derived data. We have devised a methodology and implemented it using an extensible software pipeline called RUNER (for Robust and Unique Nomenclature for Enhanced Reproducibility) that creates a robust and standardized computational process. The pipeline combines a web service and a graphical user interface (GUI) to enable seamless modifications and verified maintenance of atom force field parameters. The GUI provides an implementation for the widely used molecular modeling software package Xplor-NIH. We describe the RUNER software and demonstrate the rationale for the pipeline through examples of structural studies of small molecules and natural products. The software, pipeline, force field parameters, and file verification data for more than 4,100 compounds (including FDA-approved drugs and natural products) are freely accessible from [].Author SummaryWe describe an automated and verifiable computational pipeline for calculating the force field parameters of small molecules. The pipeline integrates several software tools and guarantees reproducibility of the parameters by utilizing a standard nomenclature across multiple computational steps and by maintaining file verification identifiers. We demonstrate the application of this pipeline to (a) processing of more than 4,100 compounds in high-throughput mode, and (b) structural studies of natural products. The graphical user interface (GUI) associated with the pipeline facilitates the manually tedious steps of force field parameters adjustments and supports visualization of the process.
doi:10.1101/429530 fatcat:huiegvgy5rdt5nwso3sgbokmti

Ligand-Specific Structural Changes in the Vitamin D Receptor in Solution

Kiran K. Singarapu, Jinge Zhu, Marco Tonelli, Hongyu Rao, Fariba M. Assadi-Porter, William M. Westler, Hector F. DeLuca, John L. Markley
2011 Biochemistry  
The inclusion bodies were solubilized in 6 M guanidinium chloride and refolded by dialysis against a buffer containing 20 mM NaH 2 PO 4 -Na 2 HPO 4 (pH 7.4), 50 mM KCl, and 2 mM DTT.  ... 
doi:10.1021/bi201637p pmid:22112050 pmcid:PMC3246842 fatcat:bolrmjrw6vfcjel5dhsee6ooku

Solution Structural Studies of GTP:Adenosylcobinamide-Phosphateguanylyl Transferase (CobY) from Methanocaldococcus jannaschii

Kiran K. Singarapu, Michele M. Otte, Marco Tonelli, William M. Westler, Jorge C. Escalante-Semerena, John L. Markley, Eugene A. Permyakov
2015 PLoS ONE  
constant of K d = 5.0 × 10 −6 M, but apo-CobY failed to bind GTP analogues, such as GMP-PNP, GMP-PCP or even GDP [9] .  ...  Results of biochemical experiments performed during the course of this work revealed that two subunits of apo-CobY bind one GTP molecule with a binding constant of K b = 2.0 × 10 −5 M -1 and a dissociation  ... 
doi:10.1371/journal.pone.0141297 pmid:26513744 pmcid:PMC4626045 fatcat:3twfuiktobc2rmmziy3iglftwy

NMR assignments of tryptophan residue in apo and holo LBD-rVDR

Wanda Sicinska, William M. Westler, Hector F. DeLuca
2005 Proteins: Structure, Function, and Bioinformatics  
II Literature Data a for Biological Activities of Analogs Compound (number) VDR binding ratio b Amount (pmol) Ca transport S/M (ICA) Serum Ca (BCM) None (control) 0 5.5 Ϯ 0.2 5.1 Ϯ 0.2  ...  Chemical Shifts of Tryptophan Indole Moiety (in ppm) a in Apo-and Holowere recorded at ϩ10°C with DSS [sodium 3-(trimethylsilyl)-1-propane sulfonate (15 M)] as the internal proton chemical shift standard  ... 
doi:10.1002/prot.20625 pmid:16130132 fatcat:ikwnvzlcofetllxnvsdc5jh5ay

Probabilistic validation of protein NMR chemical shift assignments

Hesam Dashti, Marco Tonelli, Woonghee Lee, William M. Westler, Gabriel Cornilescu, Eldon L. Ulrich, John L. Markley
2016 Journal of Biomolecular NMR  
Data validation plays an important role in ensuring the reliability and reproducibility of studies. NMR investigations of the functional properties, dynamics, chemical kinetics, and structures of proteins depend critically on the correctness of chemical shift assignments. We present a novel probabilistic method named ARECA for validating chemical shift assignments that relies on the nuclear Overhauser effect (NOE) data. ARECA has been evaluated through its application to 26 case studies and has
more » ... been shown to be complementary to, and usually more reliable than, approaches based on chemical shift databases. ARECA is available online at http://
doi:10.1007/s10858-015-0007-8 pmid:26724815 pmcid:PMC4744101 fatcat:ibsxfi3mvvfnhhk4t7cyiyzxza

Integrative NMR for biomolecular research

Woonghee Lee, Gabriel Cornilescu, Hesam Dashti, Hamid R. Eghbalnia, Marco Tonelli, William M. Westler, Samuel E. Butcher, Katherine A. Henzler-Wildman, John L. Markley
2016 Journal of Biomolecular NMR  
NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well as for observing their intermolecular interactions in real-time. However, complex steps associated with its practice have made the approach daunting for non-specialists. We introduce an NMR platform that makes biomolecular NMR spectroscopy much more accessible by integrating tools, databases, web services, and video tutorials that can be launched by
more » ... installation of NMRFAM software packages or using a cross-platform virtual machine that can be run on any standard laptop or desktop computer. The software package can be downloaded freely from the NMRFAM software download
doi:10.1007/s10858-016-0029-x pmid:27023095 pmcid:PMC4861749 fatcat:tktkhzb4xncntf4l4jxos52e4e

Applications of Parametrized NMR Spin Systems of Small Molecules

Hesam Dashti, Jonathan R. Wedell, William M. Westler, Marco Tonelli, David Aceti, Gaya K. Amarasinghe, John L. Markley, Hamid R. Eghbalnia
2018 Analytical Chemistry  
We have developed technology for producing accurate spectral fingerprints of small molecules through modeling of NMR spin system matrices to encapsulate their chemical shifts and scalar couplings. We describe here how libraries of these spin systems utilizing unique and reproducible atom numbering can be used to improve NMR-based ligand screening and metabolomics studies. We introduce new Web services that facilitate the analysis of NMR spectra of mixtures of small molecules to yield their
more » ... ification and quantification. The library of parametrized compounds has been expanded to cover simulations of 1 H NMR spectra at a variety of magnetic fields of more than 1100 compounds, included are many common metabolites and a library of drug-like molecular fragments used in ligand screening. The compound library and related Web services are freely available from SUMMARY The current release of the GISSMO library contains optimized spin system matrices corresponding to more than 1100 compounds. These include common metabolites and molecular fragments routinely utilized in ligand screening investigations. Recently implemented Web services provide tools for identifying compounds from 1 H NMR spectra collected at a wide variety of magnetic field strengths and for verifying analyses of compounds and their concentrations in 1 H NMR spectra of mixtures. Abstract * Corresponding Authors
doi:10.1021/acs.analchem.8b02660 pmid:30125102 pmcid:PMC6201686 fatcat:2jg626y73nfmrnxr7r77ac4r6u

Templated Collagen "Double Helices" Maintain Their Structure

I. Caglar Tanrikulu, William M. Westler, Aubrey J. Ellison, John L. Markley, Ronald T. Raines
2020 Journal of the American Chemical Society  
T m of the construct determined by CD is indicated in red.  ...  The T m value and the maximum CD signal for x-y follows the patterns established previously for x-y·s2 triple helices ( Figure 4 ).  ... 
doi:10.1021/jacs.9b07583 pmid:31895554 pmcid:PMC6995331 fatcat:plriemen2fdevdx5hrytv22km4
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