Evidence map›Paper›PMID 24525125›Full record

ArticleBiochemical and biophysical research communications2014

Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.

Steffen Lindert, Innokentiy Maslennikov, Ellis J C Chiu, Levi C Pierce, J Andrew McCammon, Senyon Choe

Open access · greenAbstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Steffen LindertDepartment of Chemistry and Biochemistry, Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Innokentiy MaslennikovStructural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA; Joint Center for Biosciences, 301-B, Songdo Smart Valley 214, Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea.
Ellis J C ChiuStructural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA.
Levi C PierceDepartment of Chemistry and Biochemistry, Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
J Andrew McCammonDepartment of Chemistry and Biochemistry, Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; NSF Center for Theoretical Biological Physics, National Biomedical Computation Resource, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Senyon ChoeStructural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA; Joint Center for Biosciences, 301-B, Songdo Smart Valley 214, Songdo-dong, Yeonsu-ku, Incheon 406-840, Republic of Korea; Drug Discovery Collaboratory, Carlsbad, CA 92008, USA. Electronic address: choe@salk.edu.
Salk Institute for Biological Studies · USUniversity of California, San Diego · US

Funding

THEORY OF BIOMOLECULAR DIFFUSIONR01GM031749 · NIGMS · UNIVERSITY OF HOUSTON · PI HUBER, GARY ALEXANDER, MCCAMMON, JAMES ANDREW · 1985 to 2022
$7.8M
High-speed NMR methods for membrane protein analysisR01GM098630 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHOE, SENYON · 2011 to 2014
$1.4M
Cell-free expression of human integral membrane proteins for structural studiesR01GM095623 · NIGMS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI CHOE, SENYON · 2010 to 2013
$1.2M
NIGMS NIH HHS GM095623NIGMS NIH HHS GM098630NIGMS NIH HHS R01 GM031749NIGMS NIH HHS R01 GM095623NIGMS NIH HHS R01 GM098630
6 · The paper itself

Abstract

About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B.

Indexed as

Drug DesignBinding SitesHumansIntracellular Signaling Peptides and ProteinsLigandsMembrane ProteinsMitochondrial ProteinsMolecular Docking SimulationNeoplasm ProteinsNuclear Magnetic Resonance, BiomolecularProtein ConformationHIGD1A protein, humanIntracellular Signaling Peptides and ProteinsLigandsMembrane ProteinsMitochondrial ProteinsNeoplasm ProteinsComputational dockingHuman membrane proteinsMolecular dynamicsNMR screening

Identifiers

PMID24525125
PMCPMC4457379
OpenAlexW1972152965

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.