Adapt-cMolGPT: A Conditional Generative Pre-Trained Transformer with Adapter-Based Fine-Tuning for Target-Specific Molecular Generation

Abstract

Small-molecule drug design aims to generate compounds that target specific proteins, playing a crucial role in the early stages of drug discovery. Recently, research has emerged that utilizes the GPT model, which has achieved significant success in various fields to generate molecular compounds. However, due to the persistent challenge of small datasets in the pharmaceutical field, there has been some degradation in the performance of generating target-specific compounds. To address this issue, we propose an enhanced target-specific drug generation model, Adapt-cMolGPT, which modifies molecular representation and optimizes the fine-tuning process. In particular, we introduce a new fine-tuning method that incorporates an adapter module into a pre-trained base model and alternates weight updates by sections. We evaluated the proposed model through multiple experiments and demonstrated performance improvements compared to previous models. In the experimental results, Adapt-cMolGPT generated a greater number of novel and valid compounds compared to other models, with these generated compounds exhibiting properties similar to those of real molecular data. These results indicate that our proposed method is highly effective in designing drugs targeting specific proteins.

Keywords

• small-molecule drug design
• generative pre-trained transformer
• SELFIES
• fine-tuning