Retrieving the biological impacts of protein-protein interactions (PPIs) is essential for target identification (Target ID) in drug development. Given the vast number of proteins involved, this process remains time-consuming and challenging. Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have supported Target ID; however, no benchmark currently exists for identifying the biological impacts of PPIs. To bridge this gap, we introduce the RAG Benchmark for PPIs (RAGPPI), a factual question-answer benchmark of 4,420 question-answer pairs that focus on the potential biological impacts of PPIs. Through interviews with experts, we identified criteria for a benchmark dataset, such as a type of QA and source. We built a gold-standard dataset (500 QA pairs) through expert-driven data annotation. We developed an ensemble auto-evaluation LLM that incorporates expert labeling characteristics, average fact–abstract similarity (F₁), and low-similarity fact counts (F₂), enabling the construction of a silver-standard dataset (3,720 QA pairs). We are committed to maintaining RAGPPI as a resource to support the research community in advancing RAG systems for drug discovery QA solutions.

Drug discovery (DD) has tremendously contributed to maintaining and improving public health. Hypothesizing that inhibiting protein misfolding can slow disease progression, researchers focus on target identification (Target ID) to find protein structures for drug binding. While Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have accelerated drug discovery, integrating models into cohesive workflows remains challenging. We conducted a user study with drug discovery researchers to identify the applicability of LLMs and RAGs in Target ID. We identified two main findings: 1) an LLM should provide multiple Protein-Protein Interactions (PPIs) based on an initial protein and protein candidates that have a therapeutic impact; 2) the model must provide the PPI and relevant explanations for better understanding. Based on these observations, we identified three limitations on previous approaches for Target ID: 1) semantic ambiguity, 2) lack of explainability, and 3) short retrieval units. To address these issues, we propose GraPPI, a large-scale knowledge graph (KG)-based retrieve-divide-solve agent pipeline RAG framework to support large-scale PPI signaling pathway exploration in understanding therapeutic impacts by decomposing the analysis of entire PPI pathways into sub-tasks focused on the analysis of PPI edges.