# EnzyCLIP: A Cross-Attention Dual Encoder Framework with Contrastive Learning for Predicting Enzyme Kinetic Constants

arXiv: https://arxiv.org/abs/2512.00379 · HTML: https://mlsanity.com/paper/2512.00379/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 9 of its 42 references that are in the map.
- First posted on arXiv 29 Nov 2025.

## Builds on (most cited first, 9 of 9)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [Mixed Precision Training](https://mlsanity.com/paper/1710.03740/) (2017)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [Large-Scale Chemical Language Representations Capture Molecular Structure and Properties](https://mlsanity.com/paper/2106.09553/) (2021)
- [Cross-Attention is All You Need: Adapting Pretrained Transformers for Machine Translation](https://mlsanity.com/paper/2104.08771/) (2021)
- [Rethinking Negative Pairs in Code Search](https://mlsanity.com/paper/2310.08069/) (2023)
- [Supervised Contrastive Learning with Hard Negative Samples](https://mlsanity.com/paper/2209.00078/) (2022)
- [EnzymeFlow: Generating Reaction-specific Enzyme Catalytic Pockets through Flow Matching and Co-Evolutionary Dynamics](https://mlsanity.com/paper/2410.00327/) (2024)

## Abstract (arXiv)

Accurate prediction of enzyme kinetic parameters is crucial for drug discovery, metabolic engineering, and synthetic biology applications. Current computational approaches face limitations in capturing complex enzyme-substrate interactions and often focus on single parameters while neglecting the joint prediction of catalytic turnover numbers (Kcat) and Michaelis-Menten constants (Km). We present EnzyCLIP, a novel dual-encoder framework that leverages contrastive learning and cross-attention mechanisms to predict enzyme kinetic parameters from protein sequences and substrate molecular structures. Our approach integrates ESM-2 protein language model embeddings with ChemBERTa chemical representations through a CLIP-inspired architecture enhanced with bidirectional cross-attention for dynamic enzyme-substrate interaction modeling. EnzyCLIP combines InfoNCE contrastive loss with Huber regression loss to learn aligned multimodal representations while predicting log10-transformed kinetic parameters. The model is trained on the CatPred-DB database containing 23,151 Kcat and 41,174 Km experimentally validated measurements, and achieved competitive performance with R2 scores of 0.593 for Kcat and 0.607 for Km prediction. XGBoost ensemble methods applied to the learned embeddings further improved Km prediction (R2 = 0.61) while maintaining robust Kcat performance.