biotech software engineers

Abstract: We propose EMBER, a structure-based framework for TCR--pMHC binding prediction that eliminates the need for a predicted docked complex, and with it the placement error that dominates such predictions. Traditional structure-based predictors utilize the co-folded complex structure of the receptor and the antigen and interpret binding from its contact surface. Consequently, every downstream feature inherits any deviation the structure-prediction tool introduced. Methodologically, EMBER folds the TCR and pMHC independently, encodes them as SE(3)-invariant residue graphs, and compares their learned representations without constructing a shared coordinate frame. A relative pose is therefore not an input of the model, so placement error cannot propagate into the prediction. Computationally, EMBER preprocesses $O(N{+}M)$ monomer folds where a complex-based predictor needs $O(NM)$ operations. Experimentally, under epitope-disjoint evaluation with six retrained baselines, EMBER is first on every metric under all four folding tools, by 0.9 to 14.4% in micro-AUROC, 18.5 to 25.3% in micro-AUPRC and 10.6 to 24.1% in MCC. Its ranking is also up to 85% more stable across folding tools.

Abstract: Agentic LLMs increasingly support scientific prediction by grounding decisions in external evidence. In biology, they promise accurate, interpretable predictions for important problems by integrating complex experimental and computational evidence. However, serialized tool results can contain hidden label shortcuts, such as dataset identifiers or template artifacts, that create apparent success without biological reasoning. To address this risk, we introduce a two-stage audit. Stage 1, Per-Tool TF-IDF Decomposition (PT2D), localizes label-predictive patterns to individual tool results while avoiding signal dilution in the concatenated tool trace. Stage 2, Token-Class Redaction, counterfactually tests whether the frozen LLM depends on the localized shortcut. We apply this audit to TCR-pMHC binding, where tool augmentation substantially outperforms a no-evidence baseline. At face value, this suggests that the LLM has learned to use scientific evidence. The audit overturns this interpretation: PT2D localizes the strongest signal to identifiers in one tool result, and redacting them reduces performance to chance. These findings show how hidden label shortcuts can masquerade as scientific reasoning or discovery, motivating source-level audits before benchmark gains are trusted.

Abstract: Generative AI has achieved remarkable success in de novo protein design, yet protein engineering typically begins with existing, characterized proteins. The primary demand is targeted local editing, e.g., engineering a specific region to optimize affinity, alter immunogenicity, or improve stability, while strictly preserving core catalytic motifs and overall scaffold integrity. However, no standardized framework currently exists for carrying out and evaluating such edits. In current generative-design workflows, researchers often need to manually specify complex low-level parameters and rely on repetitive, trial-and-error sampling and evaluation across generative backends to search for viable conformations. While large language models (LLMs) offer an intuitive interface to express these goals using natural language, prevailing structure-generation models cannot directly interpret high-level human instructions. To bridge this gap, we introduce PROTEAN, a standardized benchmark for text-guided protein structural editing. PROTEAN comprises 380 sub-tasks spanning six intervention families and evaluates a two-stage pipeline in which an LLM translates natural-language goals into backend-specific geometric constraints and a generative model remodels the protein backbone. A two-tier evaluation separates geometric compliance, including target attainment and off-target scope fidelity, from biophysical realizability assessed by inverse folding and refolding consistency. Across five frontier LLMs paired with three backends, strict end-to-end biophysical success starts at just 7.0%. Ablation studies show that LLM constraint compilation is already highly accurate, whereas the main bottlenecks are backend-specific scope leakage and refolding failure. PROTEAN provides an open testbed for developing autonomous, multi-backend macromolecular design agents.

Abstract: As agents rapidly evolve, existing benchmarks can become saturated, limiting their ability to distinguish capabilities and reveal remaining failure modes. Particularly in scientific domains, constructing and updating benchmarks requires substantial time, labor, and domain expertise, making it difficult to keep evaluation aligned with advances in agent capabilities. We address this challenge by investigating whether scientific-agent benchmarks can be automatically generated and iteratively adapted as agent capabilities evolve. We introduce AutoSciBench, a framework that represents each task as a high-level concept specifying the scientific domain, data modality, and required reasoning approach, together with a low-level recipe specifying how the question, environment, and ground-truth answer are constructed and verified. Agents attempt to solve each task, producing solver trajectories and corresponding judge feedback which AutoSciBench uses to revise the recipe or concept, closing observed shortcuts and shifting tasks toward raw-data re-examination, interpretation of intermediate results, and evidence integration. Experience distilled from completed refinement trajectories further guides new concept generation, allowing lessons from earlier task refinement to inform subsequent benchmark construction. Starting from existing benchmarks, we evaluate AutoSciBench across computational biology, materials science, and clinical imaging. Generated benchmarks reduce average solver accuracy by 22.4 and 25.5 percentage points relative to the human-curated benchmarks in computational biology and materials science, respectively, while generated tasks receive higher average quality ratings across all three domains, suggesting that scientific-agent evaluation can adapt as agent capabilities advance.

Abstract: Protein Language Models (PLMs) have made remarkable progress following scaling laws established in natural language processing across sequence- and structure-based tasks, yet the potential of tokenization remains underexploited. Unlike human language, proteins preserve structure despite extensive sequence variation a property standard tokenization strategies fundamentally fail to capture. We introduce ZEST (Zoned Encoding of Sequence Traits), an evolution-informed vocabulary derived from conserved regions of multiple sequence alignments. ZEST allows embedding domain-level biological priors directly at the tokenization stage rather than learning them implicitly through scale. ZEST natively compresses sequences to an average token length of 4 residues, enabling our model to process 4,000 residues within a standard 1024-token context window. Building on this, we present LEMON (Layered Extraction of Molecular Ordering from Nature), a compact 200M-parameter sequence-based model for detection of remote homology between protein sequences trained on a single H100 GPU for one week. Despite its modest size, LEMON outperforms state-of-the-art models ranging from 600M to 3B parameters. Our results demonstrate that evolution-informed tokenization can substitute for massive parameter scaling, opening a new direction for efficient, biologically-grounded protein representation learning. All code, model weights, and results are publicly available under the MIT license.