Molecular Embedding-Based Algorithm Selection in Protein-Ligand Docking

Fuente: arXiv
Salvato in:
Dettagli Bibliografici
Autori principali: Wang, Jiabao Brad, Cao, Siyuan, Wu, Hongxuan, Yuan, Yiliang, Misir, Mustafa
Natura: Preprint
Pubblicazione: 2025
Soggetti:
Accesso online:
Tags: Aggiungi Tag
Nessun Tag, puoi essere il primo ad aggiungerne!!
_version_ 1866914621123723264
author Wang, Jiabao Brad
Cao, Siyuan
Wu, Hongxuan
Yuan, Yiliang
Misir, Mustafa
author_facet Wang, Jiabao Brad
Cao, Siyuan
Wu, Hongxuan
Yuan, Yiliang
Misir, Mustafa
contents Selecting an effective docking algorithm is highly context-dependent, and no single method performs reliably across structural, chemical, and protocol regimes. MolAS is a lightweight algorithm-selection model that predicts per-algorithm performance from pretrained protein and ligand embeddings using attentional pooling and a shallow residual decoder. With hundreds to a few thousand labelled complexes, MolAS achieves up to a 15 percentage-point absolute improvement over the single-best solver (SBS) and closes 17--66\% of the Virtual Best Solver (VBS)--SBS gap across five docking benchmarks. Analyses of selection frequencies, margin-conditioned reliability, and benchmark-level oracle structure indicate that MolAS is most effective when the workflow-defined oracle landscape has low winner entropy and a reasonably separable top-solver region, but degrades under protocol mismatch that shifts solver rankings and changes the induced labels. These results suggest that, in the evaluated regime, robustness is limited less by representational capacity than by workflow- and protocol-induced instability in solver hierarchies, positioning MolAS as an in-domain selector for fixed pipelines and as a diagnostic tool for assessing when docking algorithm selection is well-posed.
format Preprint
id arxiv_https___arxiv_org_abs_2512_02328
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Molecular Embedding-Based Algorithm Selection in Protein-Ligand Docking
Wang, Jiabao Brad
Cao, Siyuan
Wu, Hongxuan
Yuan, Yiliang
Misir, Mustafa
Quantitative Methods
Machine Learning
Selecting an effective docking algorithm is highly context-dependent, and no single method performs reliably across structural, chemical, and protocol regimes. MolAS is a lightweight algorithm-selection model that predicts per-algorithm performance from pretrained protein and ligand embeddings using attentional pooling and a shallow residual decoder. With hundreds to a few thousand labelled complexes, MolAS achieves up to a 15 percentage-point absolute improvement over the single-best solver (SBS) and closes 17--66\% of the Virtual Best Solver (VBS)--SBS gap across five docking benchmarks. Analyses of selection frequencies, margin-conditioned reliability, and benchmark-level oracle structure indicate that MolAS is most effective when the workflow-defined oracle landscape has low winner entropy and a reasonably separable top-solver region, but degrades under protocol mismatch that shifts solver rankings and changes the induced labels. These results suggest that, in the evaluated regime, robustness is limited less by representational capacity than by workflow- and protocol-induced instability in solver hierarchies, positioning MolAS as an in-domain selector for fixed pipelines and as a diagnostic tool for assessing when docking algorithm selection is well-posed.
title Molecular Embedding-Based Algorithm Selection in Protein-Ligand Docking
topic Quantitative Methods
Machine Learning
url https://arxiv.org/abs/2512.02328