AI-Assisted Scientific Research

Many molecular Transformers lack probabilistic latent variables for posterior inference and latent interpolation. We introduce STAR-VAE, a SELFIES-encoded, Transformer-based, AutoRegressive Variational AutoEncoder combining a bidirectional encoder with an autoregressive decoder pretrained on 79 million PubChem molecules. A property signal jointly conditions the prior, posterior, and decoder, while LoRA adapters support fine-tuning on small datasets without modifying the backbone. STAR-VAE achieves 100% validity and near-perfect novelty under unconditional MOSES sampling, the lowest KL divergence on five of ten GuacaMol descriptors, Spearman \r{ho} = 0.62 at 98% validity for synthetic-accessibility conditioning, and directional docking-score control for three Tartarus protein targets. Across four ChEMBL targets, seed-based posterior sampling recovers target-associated held-out scaffolds while label-conditioned sampling produces structurally diverse outputs. Code is available at https://github.com/BiomedSciAI/STAR-VAE.

Large language models (LLMs) have demonstrated significant potential to accelerate scientific discovery as valuable tools for analyzing data, generating hypotheses, and supporting innovative approaches in various scientific fields. In this work, we investigate how LLMs can handle the transition from conceptual research ideas to well-structured research plans. Effective research planning not only supports scientists in advancing their research but also represents a crucial capability for the development of autonomous research agents. Despite its importance, the field lacks a systematic understanding of LLMs' research planning capability. To rigorously measure this capability, we introduce the Idea2Plan task and Idea2Plan Bench, a set of benchmarks built from ICML 2025 and Nature Mental Health papers released after major LLM training cutoffs. Each benchmark instance includes a research idea and a grading rubric capturing the key components of valid plans. We further propose Idea2Plan JudgeEval, a complementary benchmark to assess the reliability of LLM-based judges against expert annotations. Experimental results show that GPT-5 achieves the strongest performance on the benchmark, though substantial headroom remains for improvement. Our study provides new insights into LLMs' capability for research planning and lays the groundwork for future progress.

Make-on-demand combinatorial synthesis libraries (CSLs) like Enamine REAL have significantly enabled drug discovery efforts. However, their large size presents a challenge for virtual screening, where the goal is to identify the top compounds in a library according to a computational objective (e.g., optimizing docking score) subject to computational constraints under a limited computational budget. For current library sizes -- numbering in the tens of billions of compounds -- and scoring functions of interest, a routine virtual screening campaign may be limited to scoring fewer than 0.1% of the available compounds, leaving potentially many high scoring compounds undiscovered. Furthermore, as constraints (and sometimes objectives) change during the course of a virtual screening campaign, existing virtual screening algorithms typically offer little room for amortization. We propose the approximate-but-exhaustive search protocol for CSLs, or APEX. APEX utilizes a neural network surrogate that exploits the structure of CSLs in the prediction of objectives and constraints to make full enumeration on a consumer GPU possible in under a minute, allowing for exact retrieval of approximate top-k sets. To demonstrate APEX's capabilities, we develop a benchmark CSL comprised of more than 10 million compounds, all of which have been annotated with their docking scores on five medically relevant targets along with physicohemical properties measured with RDKit such that, for any objective and set of constraints, the ground truth top-k compounds can be identified and compared against the retrievals from any virtual screening algorithm. We show APEX's consistently strong performance both in retrieval accuracy and runtime compared to alternative methods.

As researchers increasingly adopt LLMs as writing assistants, generating high-quality research paper introductions remains both challenging and essential. We introduce Scientific Introduction Generation (SciIG), a task that evaluates LLMs' ability to produce coherent introductions from titles, abstracts, and related works. Curating new datasets from NAACL 2025 and ICLR 2025 papers, we assess five state-of-the-art models, including both open-source (DeepSeek-v3, Gemma-3-12B, LLaMA 4-Maverick, MistralAI Small 3.1) and closed-source GPT-4o systems, across multiple dimensions: lexical overlap, semantic similarity, content coverage, faithfulness, consistency, citation correctness, and narrative quality. Our comprehensive framework combines automated metrics with LLM-as-a-judge evaluations. Results demonstrate LLaMA-4 Maverick's superior performance on most metrics, particularly in semantic similarity and faithfulness. Moreover, three-shot prompting consistently outperforms fewer-shot approaches. These findings provide practical insights into developing effective research writing assistants and set realistic expectations for LLM-assisted academic writing. To foster re- producibility and future research, we publicly release all code and datasets.

Chemical Language Models (CLMs) are increasingly used in de novo drug design, driven by recent growth in model scale, compute, and dataset size. However, the relationship between design choices, training dynamics, and downstream generation quality remains poorly understood. We present a compute-controlled scaling study of CLMs comprising more than 30,000 experiments across molecular representations (SMILES, SELFIES, SAFE), tokenizations (atom-level and byte-pair encoding), model scales (0.5M-1B parameters), leakage-controlled datasets (MOSES, ChEMBL, PubChem, ZINC-22), and architectures (decoder-only and encoder-decoder). By fitting IsoFLOP profiles, we establish clear scaling trends in pretraining loss, but find that these improvements do not translate into comparable gains in goal-directed molecular design. Layer-wise probing and sparse autoencoder analysis reveal continued development of chemical representations: chemical syntax saturates early, while semantic properties emerge more slowly and become increasingly accessible with further training and model scale. These representational gains coexist with diminishing improvements in goal-directed generation under the evaluated protocols and oracle budgets. Our resulting suite of models, NovoMolGen, achieves state-of-the-art results, outperforming prior CLMs and specialized generative models in goal-directed molecular generation across drug discovery tasks. These findings expose a disconnect between chemical representation learning and downstream molecular design, motivating the development of pretraining paradigms that more directly learn chemical semantics.

Large language models (LLMs) are beginning to reshape how organic-synthesis workflows are represented, queried, planned, and connected to experimental automation. Assessing their contribution is not straightforward because reaction-specific transformers, chemistry-adapted LLMs, tool-using agents, optimizers, and autonomous laboratories are often discussed under the same broad terminology despite operating at different levels of the synthesis workflow. This Review traces the progression from reaction prediction and retrosynthetic planning to reaction development, literature-to-protocol translation, and robotic execution, with representative numerical claims verified against primary sources available through 4 September 2026. We examine where language models provide genuine added value, where established specialist methods remain the principal source of performance, and how retrieval, uncertainty-aware optimization, deterministic chemistry tools, robotics, sensing, and human oversight alter system behavior. The evidence shows a clear transition from isolated language-model demonstrations toward modular scientific systems that combine broad language priors with specialized computation and experimentally grounded feedback. Emerging work on multimodal reaction understanding, standardized tool interoperability, provenance-aware execution, and programmable laboratory infrastructure extends this transition further. Despite this progress, reliable deployment continues to depend on generalization beyond historical reaction corpora, calibrated uncertainty, transparent component attribution, safety controls, reproducible system state, and prospective experimental validation.

Large Reasoning Models (LRMs) have made significant progress in mathematical capabilities in recent times. However, these successes have been primarily confined to competition-level problems. In this work, we propose AI Mathematician (AIM) framework, which harnesses the reasoning strength of LRMs to support frontier mathematical research. We have identified two critical challenges of mathematical research compared to competition, the intrinsic complexity of research problems and the requirement of procedural rigor. To address these challenges, AIM incorporates two core strategies: an exploration mechanism to foster longer solution paths, and the pessimistic reasonable verification method to ensure reliability. This early version of AIM already exhibits strong capability in tackling research-level tasks. We conducted extensive experiments across several real-world mathematical topics and obtained promising results. AIM is able to autonomously construct substantial portions of proofs and uncover non-trivial insights within each research area. These findings highlight the potential of LRMs in mathematical discovery and suggest that LRM-based agent systems could significantly accelerate mathematical research in the future.

Scientific language is a central infrastructure of knowledge production, but it remains unclear whether large language models (LLMs) are altering not only how scientists write, but also how scientific knowledge is communicated and accessed. Here we analyze 21.36 million scientific abstracts published between 2020 and 2024, together with historical records from major journals, to trace recent changes in the language of science. We identify a marked turning point in 2024, when scientific writing shows a sharp increase in lexical complexity alongside a decline in syntactic complexity. This shift is pervasive across disciplines and journal tiers, and is more pronounced in texts by scholars working in non-native English contexts, especially those from language backgrounds that differ more typologically from English. Controlled polishing experiments confirm that LLMs reproduce this pattern by favoring more lexically dense and syntactically compressed expression. We further show why this linguistic shift matters: it may widen the distance between scientific discourse and public-facing language, while also helping scholars in non-native English contexts navigate English-language publishing requirements. These findings suggest that LLMs may broaden participation in scientific authorship while narrowing the accessibility of scientific communication, making them a new force in the linguistic infrastructure of science.

Background: Neurosymbolic (NeSy) artificial intelligence describes the combination of logic or rule-based techniques with neural networks. Compared to neural approaches, NeSy methods often possess enhanced interpretability, which is particularly promising for biomedical applications like drug discovery. However, no clear guidelines exist to assess the biological plausibility of model interpretations. Methods: To assess interpretability in the context of drug discovery, we devise a novel prediction task, called drug mechanism-of-action (MoA) deconvolution, with an associated, tailored knowledge graph (KG), MoA-net. We then develop the MoA Retrieval System (MARS), a NeSy approach for drug discovery which leverages logical rules with learned rule weights. Results: Using MARS' interpretable features alongside domain knowledge, we find that MARS and other NeSy approaches on KGs are susceptible to reasoning shortcuts, in which the prediction of true labels is driven by ``degree-bias'' rather than the domain-based rules. Subsequently, we demonstrate ways to identify and mitigate this. Thereafter, MARS achieves performance on par with current state-of-the-art models while producing model interpretations aligned with known MoAs. Conclusion: Through MARS, we showcase the novel task of computational MoA deconvolution. Our results emphasize the importance of using interpretable models, like NeSy ones, for applications in drug discovery. Specifically, by identifying and mitigating reasoning shortcuts, MARS MoA predictions which are biologically meaningful and, therefore, more reliable for downstream drug discovery research.

Molecular optimization, the process of designing molecules with desirable properties, represents a critical challenge in drug discovery. The recent advancements in large language models (LLMs) have opened new opportunities for their integration with traditional molecular optimization algorithms to improve performance. In this work, we propose Molecular Language Model powered Evolutionary Algorithm (Mol-E), an evolutionary algorithm that relies on the generative capabilities of LLMs trained on molecules and molecular properties. Scientific Contribution. Mol-E obtains the highest aggregate Top-10 AUC among the comparable full-23-task results considered here, scoring 17.500 in the task-agnostic regime, in which the oracle is treated strictly as a black box, and 20.551 in the task-informed regime, in which the optimizer receives a fixed semantic description of the objective. Mol-E also improves over the evaluated baselines on multi-property optimization with docking against DRD2, MK2, and AChE.

The rapid growth of scientific literature makes it increasingly challenging for researchers to identify novel and impactful ideas, especially across disciplines. Modern artificial intelligence (AI) systems offer new opportunities for scientific ideation, but how compelling are AI-generated ideas, and how can their quality be improved? Here, we introduce SciMuse, which generates personalized research ideas using a knowledge graph of 58 million papers and a large language model (LLM). A central focus of this work is to understand how interesting these ideas are. Therefore, we conducted a large-scale evaluation in which more than 100 research group leaders -- spanning the natural sciences to the humanities -- rated over 4,400 personalized ideas according to their level of interest. Overall, expert ratings were modest (mean 2.40 on a 5-point scale, most common rating 1), while 24.9% of ideas were rated 4 or 5. We find that supplying concept pairs selected using the knowledge graph does not improve expert-rated interest over a titles-only GPT baseline. High-citation-predicted pairs even showed a weak tendency (1.94$σ$) toward lower interest than random pairs. Nevertheless, graph features can be used to control properties of ideas, and, using this unique evaluation dataset, we show that idea interest can be predicted with both a supervised neural network based on graph features and a zero-shot ranking approach based on an LLM. Our work provides an AI methodology for generating scientific ideas and a large-scale interdisciplinary expert evaluation, paving the way to study and improve difficult-to-measure metrics such as expert-perceived scientific interestingness.

Machine learning theory studies learning procedures through mathematical setups in which the data model, training protocol, oracle access, loss, metric, and randomness define the phenomenon that a theorem is meant to explain. Solving an open problem therefore requires the problem formulation, theorem target, and proof mechanism to be developed in concert. Researchers formulate hypotheses, test them through preliminary theoretical or empirical analysis, and refine both assumptions and proofs. We investigate whether this process can be organized as an autonomous agentic workflow for ML theory research. We develop VALG, an agentic system that combines multi-level Verification, Adaptive formulation of Learning-theory problems, and Graph-structured proof development. Within each source-relative theorem branch, VALG maintains a fixed mathematical specification, checks the theorem-level composition of a typed proof-dependency graph, and constructs and reviews local proofs in dependency order. When a proof attempt fails, VALG identifies whether the obstruction lies in a derivation, the proof structure, or the theorem formulation and routes the next attempt accordingly. Formulation-level obstructions initiate an explicitly related variant or relaxation, preserving the mathematical relation between the resulting theorem and the source problem. We evaluate VALG on nine subproblems from five COLT 2026 open problems. Two runs produce internally finalized theorem candidates that match the scope of their source briefs; the remaining seven yield restricted-method results, special cases, or conditional theorems. These case studies show how VALG keeps source-scope matches, relaxations, conditional results, and blocked attempts mathematically distinct. VALG is open source at https://github.com/DechenZhang/VALG-ML-Theory-Agent.