# PepLLM: ESM-Guided Llama for Structured Protein-Peptide Binding Interface Analysis

arXiv: https://arxiv.org/abs/2608.21367 · HTML: https://mlsanity.com/paper/2608.21367/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 3 of its 13 references that are in the map.
- First posted on arXiv 18 Jun 2026.

## Builds on (most cited first, 3 of 3)

- [ProLLaMA: A Protein Large Language Model for Multi-Task Protein Language Processing](https://mlsanity.com/paper/2402.16445/) (2024)
- [ProtLLM: An Interleaved Protein-Language LLM with Protein-as-Word Pre-Training](https://mlsanity.com/paper/2403.07920/) (2024)
- [EvoLlama: Enhancing LLMs' Understanding of Proteins via Multimodal Structure and Sequence Representations](https://mlsanity.com/paper/2412.11618/) (2024)

## Abstract (arXiv)

Protein-peptide interactions are central to cellular regulation and peptide-based drug discovery, yet existing computational methods mainly focus on interaction classification, binding-site prediction, or peptide binder generation. These formulations provide limited insight into the physicochemical mechanisms that determine how a peptide binds to a protein. In this work, we introduce PepLLM, an instruction-tuned framework for structured protein-peptide interface understanding. Given protein-peptide sequences, PepLLM generates a machine-readable JSON annotation describing multiple interface properties, including peptide burial state, hydrogen-bond density, salt-bridge presence, hotspot residues, hydrophobicity, and electrostatic complementarity. To support this task, we construct a new protein-peptide interface dataset by integrating structural interface analysis, solvent-accessible surface area computation, hydrophobic burial estimation, electrostatic potential calculation, and redundancy-aware data splitting. PepLLM connects a pretrained ESM encoder with a LLaMA decoder through a nonlinear modality adapter. The adapted ESM residue embeddings are injected into the LLaMA prompt as continuous soft tokens via placeholder-token replacement, enabling the decoder to generate structured interface annotations under instruction tuning. By moving beyond single-label prediction toward multi-property and mechanism-aware generation, PepLLM establishes a new task and modeling paradigm for interpretable protein-peptide interface analysis.