Design Proteins Using Large Language Models: Enhancements and Comparative Analyses

Kamyar Zeinalipour, Neda Jamshidi, Monica Bianchini, Marco Maggini, Marco Gori

Keywords: Protein generation, Pre-trained LLMs, Natural Language Processing, Protein Design, Generative Models for Proteins

Abstract:

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the generation of high-quality protein sequences. Specifically, we adopt a suite of pre-trained LLMs, including Mistral-7B (https://huggingface.co/Kamyar-zeinalipour/P-Mistral-7B), Llama-2-7B (https://huggingface.co/Kamyar-zeinalipour/P-Llama2-7B), Llama-3-8B (https://huggingface.co/Kamyar-zeinalipour/P-Llama3-8B), and gemma-7B (https://huggingface.co/Kamyar-zeinalipour/P-gemma-7B), to produce valid protein sequences. All of these models are publicly available (https://github.com/KamyarZeinalipour/protein-design-LLMs).

Unlike previous work in this field, our approach utilizes a relatively small dataset comprising 42,000 distinct human protein sequences. We retrain these models to process protein-related data, ensuring the generation of biologically feasible protein structures. Our findings demonstrate that even with limited data, the adapted models exhibit efficiency comparable to established protein-focused models such as ProGen varieties, ProtGPT2, and ProLLaMA, which were trained on millions of protein sequences. To validate and quantify the performance of our models, we conduct comparative analyses employing standard metrics such as pLDDT, RMSD, TM-score, and REU. Furthermore, we commit to making the trained versions of all four models publicly available, fostering greater transparency and collaboration in the field of computational biology.

Archival Option: The authors of this submission want it to appear in the archival proceedings.

Submission Number: 4