SurfDiff: protein surface profiling for selective or broadly reactive epitope prioritisation in binder and immunogen design.

ABSTRACT: Rational selection of protein-surface patches - epitopes or ligandable sites - is essential for developing targeted antibodies, binding proteins, peptides, or small-molecule ligands, and for informing immunogen design in vaccines. We present SurfDiff, a structure- and sequence-informed framework for protein surface comparison. SurfDiff supports one-to-one and one-to-many comparisons by combining local structural alignments with physicochemically and spatially aware neighbourhood analysis. It assigns residue-level uniqueness and similarity scores, which can be aggregated into surface-level similarity, selectivity, and a discriminability score that captures conservation across desired targets while penalising similarity to undesired off-targets. These scores, calculated solely from the targe

SUBMITTER: Jedlitzke B 

PROVIDER: S-EPMC12776457 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature