De Novo Protein Binder Design Pipeline

Overview

This pipeline designs novel protein binders for a target protein structure through six phases:

1. Target Preparation -- Clean and validate the input PDB
2. Epitope Selection -- Identify binding sites via PeSTo + DBSCAN clustering
3. Binder Length Optimization -- Calculate optimal binder size from epitope geometry
4. Backbone Generation -- Generate candidate scaffolds with RFdiffusion
5. Sequence Design -- Design sequences via inverse folding (ProteinMPNN / ESM-IF1)
6. Validation -- Multi-metric screening with early termination
7. Round Advancement -- Iterate or finalize based on results

Interaction Model

Phases 0--1.5 (preparation): Run autonomously -- clean the target, select epitopes, determine binder length. No user approval needed.

Before Phase 2 (backbone generation): Present a design plan to the user summarizing: target info, selected epitope and hotspot residues, proposed binder length, number of backbones, and any concerns (large target, polar epitope, etc.). Wait for user approval before proceeding.