SurfPro: Functional Protein Design Based on Continuous Surface

TL;DR

SurfPro is a novel protein design method that generates functional proteins from desired surface features by modeling geometric and biochemical properties, outperforming previous inverse folding techniques.

Contribution

Introduces SurfPro, a hierarchical encoder-decoder framework that integrates geometric and biochemical surface features for functional protein design.

Findings

Achieves 57.78% recovery rate on CATH 4.2 benchmark.

Outperforms previous inverse folding methods.

Shows higher success in protein binder and enzyme design tasks.

Abstract

How can we design proteins with desired functions? We are motivated by a chemical intuition that both geometric structure and biochemical properties are critical to a protein's function. In this paper, we propose SurfPro, a new method to generate functional proteins given a desired surface and its associated biochemical properties. SurfPro comprises a hierarchical encoder that progressively models the geometric shape and biochemical features of a protein surface, and an autoregressive decoder to produce an amino acid sequence. We evaluate SurfPro on a standard inverse folding benchmark CATH 4.2 and two functional protein design tasks: protein binder design and enzyme design. Our SurfPro consistently surpasses previous state-of-the-art inverse folding methods, achieving a recovery rate of 57.78% on CATH 4.2 and higher success rates in terms of protein-protein binding and enzyme-substrate interaction scores.