arXiv subjects

Mingran Cao

Publications and source records attributed to Mingran Cao.

2 recordsLinked to original sources

arXiv2026

ProteoCraft: Protein Design as Proposal-Verification Search

Protein-protein interactions underpin nearly all biological processes. Yet, designing proteins with desired interactions remains challenging due to the structural complexity governing molecular recognition. This study views protein design as a search optimization problem over a combinatorial sequence space under expensive structural evaluation. Toward this goal, we introduce a novel tree-based search framework, ProteoCraft, that employs approximate structural gradients from diffusion-based structure predictors as effective proposal policies to specify where the search should explore. Complete no-gradient inference of folding models separately assigns values to the resulting sequences, determining what is good. ProteoCraft allocates this verification budget through a coarse-to-fine paradigm: multi-site edits first explore distinct sequence basins, then verified promising states undergo strict single-site refinement. Across fourteen de novo binder-design settings spanning eight target proteins, five immune-relevant TCR-facing targets, and four localized CDR redesign tasks, ProteoCraft improves design quality and high-confidence yield. These improvements persist under independent AF2-IG and Rosetta-based interface evaluation. Prospective experimental validation further yielded an 82.9% binding hit rate for PD-L1 miniproteins, with a best measured KD of 0.879 nM, and confirmed binding of designed IFNAR2 VHH. Our code is available at https://github.com/smiles724/ProteoCraft_v1.

cs.CE↗

arXiv2024

Benchmarking Out-of-Distribution Generalization Capabilities of DNN-based Encoding Models for the Ventral Visual Cortex

We characterized the generalization capabilities of DNN-based encoding models when predicting neuronal responses from the visual cortex. We collected \textit{MacaqueITBench}, a large-scale dataset of neural population responses from the macaque inferior temporal (IT) cortex to over $300,000$ images, comprising $8,233$ unique natural images presented to seven monkeys over $109$ sessions. Using \textit{MacaqueITBench}, we investigated the impact of distribution shifts on models predicting neural activity by dividing the images into Out-Of-Distribution (OOD) train and test splits. The OOD splits included several different image-computable types including image contrast, hue, intensity, temperature, and saturation. Compared to the performance on in-distribution test images -- the conventional way these models have been evaluated -- models performed worse at predicting neuronal responses to out-of-distribution images, retaining as little as $20\%$ of the performance on in-distribution test images. The generalization performance under OOD shifts can be well accounted by a simple image similarity metric -- the cosine distance between image representations extracted from a pre-trained object recognition model is a strong predictor of neural predictivity under different distribution shifts. The dataset of images, neuronal firing rate recordings, and computational benchmarks are hosted publicly at: https://bit.ly/3zeutVd.

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