Biology subjects

Errington, D.

Publications and source records attributed to Errington, D..

3 recordsLinked to original sources

bioRxiv2026

Nesso-1: Accelerating Open-Source Binding Affinity Predictions

In this technical report, we introduce NO_SCPLOWESSOC_SCPLOW-1, a coarse-grained cofolding framework for binding- affinity prediction. NO_SCPLOWESSOC_SCPLOW-1 requires[~] 1 second per prediction on a single GPU. This offers more than one order of magnitude speed-up over the leading open-source baseline, Boltz-2, which significantly expands the regions of chemical space that can be explored during high-throughput virtual screening. Importantly, NO_SCPLOWESSOC_SCPLOW-1 matches or surpasses the accuracy of Boltz-2 over the same benchmarks adopted in their study--which we show reflect in-distribution scenarios--as well as over more challenging out-of-distribution data encompassing the OpenBind affinity benchmark and 25 internal biochemical assays. Notably, NO_SCPLOWESSOC_SCPLOW-1 maintains robust predictive accuracy even on assays with extremely low similarity to the training data. Moreover, we highlight examples where NO_SCPLOWESSOC_SCPLOW-1 demonstrates meaningful selectivity, separating the binding affinities of identical compounds between on-targets and related off-targets. Nonetheless, zero-shot generalization to real- world medicinal chemistry remains an inherently challenging task; consequently, we acknowledge specific assays where the models performance is limited. We open-source NO_SCPLOWESSOC_SCPLOW-1: code and weights are available at https://github.com/recursionpharma/nesso

molecular biology↗

bioRxiv2026

Modelling antibody structures at the speed of language

Protein structure prediction is currently substantially slower than obtaining sequence representations of proteins. This leads to most property prediction methods relying solely on trivial or learned sequence embeddings. However, contemporary structure prediction and sequence models are both based on Transformers, and structure prediction models often have fewer parameters, suggesting that there might be domains where accurate structure prediction adds no practical overhead to sequence-only modelling. Here, we demonstrate this can be achieved for adaptive immune proteins by introducing FlashABB, which predicts highly accurate antibody structures, and does so faster than even modestly-sized language models can embed sequences. As a component of FlashABB, we develop Flashpoint Attention, a fast and linear memory analog of Invariant Point Attention. To our knowledge, FlashABB is the first example of a model that accurately predicts protein structure faster than protein language models can generate embeddings, enabling efficient access to 3D information without the need for precomputed structures. Using FlashABB, we develop methods for predicting antibody stability and developability which can be scaled to repertoires of millions of sequences. Our results show how the computational bottleneck of protein structure prediction can be removed in some real-world cases. The code and model weights for FlashABB are available on GitHub: https://github.com/oxpig/FlashABB

molecular biology↗

bioRxiv2024

Computational design of developable therapeutic antibodies: efficient traversal of binder landscapes and rescue of escape mutations

Developing therapeutic antibodies is a challenging endeavour, often requiring large-scale screening to produce initial binders, that still often require optimisation for developability. We present a computational pipeline for the discovery and design of therapeutic antibody candidates, which incorporates physics- and AI-based methods for the generation, assessment, and validation of developable candidate antibodies against diverse epitopes, via efficient few-shot experimental screens. We demonstrate that these orthogonal methods can lead to promising designs. We evaluated our approach by experimentally testing a small number of candidates against multiple SARS-CoV-2 variants in three different tasks: (i) traversing sequence landscapes of binders, we identify highly sequence dissimilar antibodies that retain binding to the Wuhan strain, (ii) rescuing binding from escape mutations, we show up to 54% of designs gain binding affinity to a new subvariant and (iii) improving developability characteristics of antibodies while retaining binding properties. These results together demonstrate an end-to-end antibody design pipeline with applicability across a wide range of antibody design tasks. We experimentally characterised binding against different antigen targets, developability profiles, and cryo-EM structures of designed antibodies. Our work demonstrates how combined AI and physics computational methods improve productivity and viability of antibody designs.

bioinformatics↗