用二值潜在空间建模蛋白质适应度,让经典优化算法高效搜索最佳序列。
Q-BIOLAT: Binary Latent Protein Fitness Landscapes for QUBO-Based Optimization
- 将蛋白质语言模型嵌入转为二值潜在表示,构建可解的二次无约束二值优化问题。
- 结构化二值表示在多个数据集上使模拟退火等算法成功找到高适应度序列。
- 揭示了不同表示对优化能力的影响,适合关注蛋白质设计与量子启发优化的研究者。
蛋白质适应度优化本质上是离散组合问题,但现有学习方法多依赖连续表征且仅以预测准确率评估。我们提出Q-BIOLAT框架,在紧凑的二值潜在空间中建模并优化蛋白质适应度景观。基于预训练蛋白语言模型嵌入,构建二值潜在表示,并学习一个捕获一阶与二阶交互的二次无约束二值优化(QUBO)代理模型。研究发现,具有相似预测性能的表征可能产生截然不同的优化景观:基于自编码器的表征经二值化后会坍缩,导致退化的潜在空间,无法支持组合搜索;而简单结构化表示如主成分分析(PCA)则生成高熵、可解码且适合优化的潜在空间。在多个数据集和数据条件下,经典组合优化方法(包括模拟退火、遗传算法、贪心爬山)在结构化二值潜在空间中表现优异。通过将目标表达为QUBO形式,本方法连接现代机器学习与离散及量子启发优化。代码与数据集已公开于:https://github.com/HySonLab/Q-BIOLAT-Extended
原文摘要 · Abstract (English)
Protein fitness optimization is inherently a discrete combinatorial problem, yet most learning-based approaches rely on continuous representations and are primarily evaluated through predictive accuracy. We introduce Q-BIOLAT, a framework for modeling and optimizing protein fitness landscapes in compact binary latent spaces. Starting from pretrained protein language model embeddings, we construct binary latent representations and learn a quadratic unconstrained binary optimization (QUBO) surrogate that captures unary and pairwise interactions. Beyond its formulation, Q-BIOLAT provides a representation-centric perspective on protein fitness modeling. We show that representations with similar predictive performance can induce fundamentally different optimization landscapes. In particular, learned autoencoder-based representations collapse after binarization, producing degenerate latent spaces that fail to support combinatorial search, whereas simple structured representations such as PCA yield high-entropy, decodable, and optimization-friendly latent spaces. Across multiple datasets and data regimes, we demonstrate that classical combinatorial optimization methods, including simulated annealing, genetic algorithms, and greedy hill climbing, are highly effective in structured binary latent spaces. By expressing the objective in QUBO form, our approach connects modern machine learning with discrete and quantum-inspired optimization. Our implementation and dataset are publicly available at: https://github.com/HySonLab/Q-BIOLAT-Extended
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