← 研踪 PaperTrailarXiv:2611.03379 · v1
RangeFinder: Predicting Ligand Property Ranges from Protein Pockets
首次提交 2026-11-03 00:21
版本更新 2026-11-03 00:21
雷达观测 2026-11-04 23:41
摘要
Identifying ligands for a protein target requires searching a vast chemical space for a comparatively small set of compatible molecules. Existing machine learning approaches primarily address this problem by generating candidate ligands or scoring individual protein-ligand pairs, but provide limited information about the broader chemical space compatible with a binding pocket. We introduce RangeFinder, an SE(3)-equivariant transformer pocket-level model, trained and evaluated on BioLiP2 data, that predicts ranges over nine physicochemical ligand properties directly from pocket structure, chemistry, and evolutionary context. Using an intersection-over-union objective and evaluation metric (range-IoU), RangeFinder achieves a range-IoU of $0.464 \pm 0.002$, outperforming all deployable baselines while requiring only $12.2$ ms per pocket. We also quantify our method's ability to reduce the ligand search space while retaining compatible binders; in this regard, RangeFinder achieves a Reduction-Recall F-Score of $0.543 \pm 0.011$ --- once again outperforming all deployable baselines. Ablation experiments indicate that RangeFinder's performance depends more strongly on the density and quality of ligand supervision than on any individual input modality or specialized training strategy. Together, these results position RangeFinder as an inexpensive and effective molecular filtering prior, with demonstrated potential in narrowing the ligand search space of target pockets before docking, generation, or synthesis. The code for this project can be found at: https://github.com/alannadels/RangeFinder.
作者备注：Accepted at the AI for Drug Discovery workshop --- NeurIPS 2026
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v1 · 2026-11-03 00:21 · 最新观测版本
RangeFinder: Predicting Ligand Property Ranges from Protein Pockets
Identifying ligands for a protein target requires searching a vast chemical space for a comparatively small set of compatible molecules. Existing machine learning approaches primarily address this problem by generating candidate ligands or scoring individual protein-ligand pairs, but provide limited information about the broader chemical space compatible with a binding pocket. We introduce RangeFinder, an SE(3)-equivariant transformer pocket-level model, trained and evaluated on BioLiP2 data, that predicts ranges over nine physicochemical ligand properties directly from pocket structure, chemistry, and evolutionary context. Using an intersection-over-union objective and evaluation metric (range-IoU), RangeFinder achieves a range-IoU of $0.464 \pm 0.002$, outperforming all deployable baselines while requiring only $12.2$ ms per pocket. We also quantify our method's ability to reduce the ligand search space while retaining compatible binders; in this regard, RangeFinder achieves a Reduction-Recall F-Score of $0.543 \pm 0.011$ --- once again outperforming all deployable baselines. Ablation experiments indicate that RangeFinder's performance depends more strongly on the density and quality of ligand supervision than on any individual input modality or specialized training strategy. Together, these results position RangeFinder as an inexpensive and effective molecular filtering prior, with demonstrated potential in narrowing the ligand search space of target pockets before docking, generation, or synthesis. The code for this project can be found at: https://github.com/alannadels/RangeFinder.
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