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Record W4409901652 · doi:10.1080/17460441.2025.2497912

Water in drug design: pitfalls and good practices

2025· review· en· W4409901652 on OpenAlexaff
Balázs Zoltán Zsidó, Csaba Hetényi

Bibliographic record

VenueExpert Opinion on Drug Discovery · 2025
Typereview
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsCentre for Drug Research and Development
FundersNational Research, Development and Innovation OfficeMagyar Tudományos Akadémia
KeywordsDrugMedicineComputer scienceRisk analysis (engineering)Intensive care medicinePharmacology

Abstract

fetched live from OpenAlex

INTRODUCTION: Structure-based drug design relies on optimizing drug-target interactions and blocking harmful pathophysiological events at the atomic level. Such events of the human body are modulated by water acting either as a medium or an individual partner in molecular interactions. A precise understanding of the modulatory mechanisms of water is essential for a successful drug design. AREAS COVERED: The present review discusses different topographical and networking situations that result in radically different roles of water, a root of various pitfalls of drug design. The review surveys good practices for tackling the problems of determining water structure at atomic resolution. Techniques for quantifying the effects of bulk, networking, and individual water molecules on the stability of drug-target complexes are also discussed. The article is based on a literature search using the PubMed, Web of Science, and Google Scholar databases. EXPERT OPINION: With advances in rapid computational algorithms and a better understanding of the physicochemical machinery of complex formation, theoretical approaches have resulted in elegant and cost-effective tools that fill the knowledge gaps left by the limited experimental methods. Overcoming the technical pitfalls of drug design, water transforms from a frustrating challenge into a handy tool for fine-tuning drug-target interactions.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Scholarly communication
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.971
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.003
Open science0.0020.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.078
GPT teacher head0.405
Teacher spread0.327 · 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 teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreReview

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

Citations6
Published2025
Admission routes1
Has abstractyes

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