Evidence map›Paper›PMID 38187746›Full record

ArticlebioRxiv : the preprint server for biology2023

Lei Lu, Xuxu Gou, Sophia K Tan, Samuel I Mann, Hyunjun Yang, Xiaofang Zhong, Dimitrios Gazgalis, Jesús Valdiviezo, Hyunil Jo, Yibing Wu and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Lei LuDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Xuxu GouHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA.
Sophia K TanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Samuel I MannDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Hyunjun YangDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Xiaofang ZhongDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Dimitrios GazgalisDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Jesús ValdiviezoDana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Hyunil JoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Yibing WuDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Morgan E DiolaitiHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA.
Alan AshworthHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA.
Nicholas F PolizziDana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
William F DeGradoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Deciphering the relationship between structure, dynamics and function in helical bundle proteinsR35GM122603 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILLIAM DEGRADO · 2017 to 2026
$7.1M
De novo design of small-molecule-binding proteinsR00GM135519 · NIGMS · DANA-FARBER CANCER INST · PI POLIZZI, NICHOLAS · 2022 to 2024
$747k
NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R00 GM135519NIGMS NIH HHS R35 GM122603
6 · The paper itself

Abstract

The de novo design of small-molecule-binding proteins has seen exciting recent progress; however, the ability to achieve exquisite affinity for binding small molecules while tuning specificity has not yet been demonstrated directly from computation. Here, we develop a computational procedure that results in the highest affinity binders to date with predetermined relative affinities, targeting a series of PARP1 inhibitors. Two of four designed proteins bound with affinities ranging from < 5 nM to low μM, in a predictable manner. X-ray crystal structures confirmed the accuracy of the designed protein-drug interactions. Molecular dynamics simulations informed the role of water in binding. Binding free-energy calculations performed directly on the designed models are in excellent agreement with the experimentally measured affinities, suggesting that the de novo design of small-molecule-binding proteins with tuned interaction energies is now feasible entirely from computation. We expect these methods to open many opportunities in biomedicine, including rapid sensor development, antidote design, and drug delivery vehicles.

Identifiers

PMID38187746
PMCPMC10769398

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.