# A decoupled alignment kernel for peptide membrane permeability predictions

arXiv: https://arxiv.org/abs/2511.21566 · HTML: https://mlsanity.com/paper/2511.21566/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 21 of its 53 references that are in the map.
- First posted on arXiv 26 Nov 2025.

## Builds on (most cited first, 21 of 21)

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## Abstract (arXiv)

Cyclic peptides are promising modalities for targeting intracellular sites; however, cell-membrane permeability remains a key bottleneck, exacerbated by limited public data and the need for well-calibrated uncertainty. Instead of relying on data-eager complex deep learning architecture, we propose a monomer-aware decoupled global alignment kernel (MD-GAK), which couples chemically meaningful residue-residue similarity with sequence alignment while decoupling local matches from gap penalties. MD-GAK is a relatively simple kernel. To further demonstrate the robustness of our framework, we also introduce a variant, PMD-GAK, which incorporates a triangular positional prior. As we will show in the experimental section, PMD-GAK can offer additional advantages over MD-GAK, particularly in reducing calibration errors. Since our focus is on uncertainty estimation, we use Gaussian Processes as the predictive model, as both MD-GAK and PMD-GAK can be directly applied within this framework. We demonstrate the effectiveness of our methods through an extensive set of experiments, comparing our fully reproducible approach against state-of-the-art models, and show that it outperforms them across all metrics.