Latent-X: An Atom-level Frontier Model for De Novo Protein Binder Design

TL;DR

Latent-X is a novel all-atom protein design model that efficiently generates high-affinity, specific protein binders directly from target epitopes, significantly advancing de novo biologics discovery.

Contribution

It introduces Latent-X, a pioneering atom-level model that jointly generates protein structures and sequences for target binding, outperforming existing methods in speed and efficacy.

Findings

Achieves over 90% hit rate for macrocyclic peptides.

Produces potent binders with low nanomolar affinities.

Generates structurally diverse binders, including complex folds.

Abstract

Traditional drug discovery relies on rounds of screening millions of candidate molecules with low success rates, making drug discovery time and resource intensive. To overcome this screening bottleneck, we introduce Latent-X, an all-atom protein design model that enables a new paradigm of precision AI design. Given a target protein epitope, Latent-X jointly generates the all atom structure and sequence of the protein binder and target, directly modelling the non-covalent interactions essential for specific binding. We demonstrate its efficacy across two therapeutically relevant modalities through extensive wet lab experiments, testing as few as 30-100 designs per target. For macrocyclic peptides, Latent-X achieves experimental hit rates exceeding 90% on all evaluated benchmark targets. For mini-binders, it consistently produces potent candidates against all evaluated benchmark targets, with binding affinities reaching the low nanomolar and picomolar range - comparable to those of approved therapeutics - whilst also being highly specific in mammalian display. In direct comparisons with the state-of-the-art models AlphaProteo, RFdiffusion and RFpeptides under identical conditions demonstrates, Latent-X generates binders with higher hit rates and better binding affinities, and uniquely creates structurally diverse binders, including complex beta-sheet folds. Its end-to-end process is an order of magnitude faster than existing multi-step computational pipelines. By drastically improving the efficiency and success rate of de novo design, Latent-X represents a significant advance towards push-button biologics discovery and a valuable tool for protein engineers. Latent-X is available at https://platform.latentlabs.com, enabling users to reliably generate de novo binders without AI infrastructure or coding.