Aligning Large Language Models and Geometric Deep Models for Protein Representation

Abstract

Latent representation alignment has become a foundational technique for constructing multimodal large language models (MLLM) by mapping embeddings from different modalities into a shared space, often aligned with the embedding space of large language models (LLMs) to enable effective cross-modal understanding. While preliminary protein-focused MLLMs have emerged, they have predominantly relied on heuristic approaches, lacking a fundamental understanding of optimal alignment practices across representations. In this study, we explore the alignment of multimodal representations between LLMs and Geometric Deep Models (GDMs) in the protein domain. We comprehensively evaluate three state-of-the-art LLMs (Gemma2-2B, LLaMa3.1-8B, and LLaMa3.1-70B) with four protein-specialized GDMs (GearNet, GVP, ScanNet, GAT). Our work examines alignment factors from both model and protein perspectives, identifying challenges in current alignment methodologies and proposing strategies to improve the alignment process. Our key findings reveal that GDMs incorporating both graph and 3D structural information align better with LLMs, larger LLMs demonstrate improved alignment capabilities, and protein rarity significantly impacts alignment performance. We also find that increasing GDM embedding dimensions, using two-layer projection heads, and fine-tuning LLMs on protein-specific data substantially enhance alignment quality. These strategies offer potential enhancements to the performance of protein-related multimodal models. Our code and data are available at https://github.com/Tizzzzy/LLM-GDM-alignment.