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Record W3012663724 · doi:10.1021/acs.jcim.9b00996

Hotspots API: A Python Package for the Detection of Small Molecule Binding Hotspots and Application to Structure-Based Drug Design

2020· article· en· W3012663724 on OpenAlexfundno aff
Peter R. Curran, Chris J. Radoux, Mihaela Smilova, Richard A. Sykes, Alícia P. Higueruelo, A.R. Bradley, Brian D. Marsden, David R. Spring, Tom L. Blundell, Andrew R. Leach, William R. Pitt, Jason C. Cole

Bibliographic record

VenueJournal of Chemical Information and Modeling · 2020
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsnot available
FundersStructural Genomics ConsortiumEngineering and Physical Sciences Research CouncilRoyal SocietyMedical Research CouncilBiotechnology and Biological Sciences Research CouncilKennedy Trust for Rheumatology ResearchUCBWellcome Trust
KeywordsPython (programming language)Computer scienceWorkflowHotspot (geology)Application programming interfaceData miningExploitDrug discoveryDatabaseBioinformaticsProgramming language

Abstract

fetched live from OpenAlex

Methods that survey protein surfaces for binding hotspots can help to evaluate target tractability and guide exploration of potential ligand binding regions. Fragment Hotspot Maps builds upon interaction data mined from the CSD (Cambridge Structural Database) and exploits the idea of identifying hotspots using small chemical fragments, which is now widely used to design new drug leads. Prior to this publication, Fragment Hotspot Maps was only publicly available through a web application. To increase the accessibility of this algorithm we present the Hotspots API (application programming interface), a toolkit that offers programmatic access to the core Fragment Hotspot Maps algorithm, thereby facilitating the interpretation and application of the analysis. To demonstrate the package's utility, we present a workflow which automatically derives protein hydrogen-bond constraints for molecular docking with GOLD. The Hotspots API is available from https://github.com/prcurran/hotspots under the MIT license and is dependent upon the commercial CSD Python API.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Software · Consensus signal: Software
Teacher disagreement score0.073
Threshold uncertainty score0.243

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0020.002
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0020.003
Open science0.0040.004
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0730.027

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.035
GPT teacher head0.278
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreSoftware

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations21
Published2020
Admission routes1
Has abstractyes

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