Binary Latent Protein Fitness Landscapes for Quantum Annealing Optimization
This work addresses protein engineering by enabling efficient combinatorial search and compatibility with quantum annealing hardware, though it appears incremental as it builds on existing methods like protein language models and classical heuristics.
The paper tackles the problem of modeling and optimizing protein fitness landscapes by proposing Q-BIOLAT, a framework that uses binary latent representations and QUBO models, and demonstrates on the ProteinGym benchmark that it captures meaningful structure and identifies high-fitness variants, with sequences retrieved in the top fraction of the training fitness distribution.
We propose Q-BIOLAT, a framework for modeling and optimizing protein fitness landscapes in binary latent spaces. Starting from protein sequences, we leverage pretrained protein language models to obtain continuous embeddings, which are then transformed into compact binary latent representations. In this space, protein fitness is approximated using a quadratic unconstrained binary optimization (QUBO) model, enabling efficient combinatorial search via classical heuristics such as simulated annealing and genetic algorithms. On the ProteinGym benchmark, we demonstrate that Q-BIOLAT captures meaningful structure in protein fitness landscapes and enables the identification of high-fitness variants. Despite using a simple binarization scheme, our method consistently retrieves sequences whose nearest neighbors lie within the top fraction of the training fitness distribution, particularly under the strongest configurations. We further show that different optimization strategies exhibit distinct behaviors, with evolutionary search performing better in higher-dimensional latent spaces and local search remaining competitive in preserving realistic sequences. Beyond its empirical performance, Q-BIOLAT provides a natural bridge between protein representation learning and combinatorial optimization. By formulating protein fitness as a QUBO problem, our framework is directly compatible with emerging quantum annealing hardware, opening new directions for quantum-assisted protein engineering. Our implementation is publicly available at: https://github.com/HySonLab/Q-BIOLAT