Identifying drug-drug interactions (DDIs) is critical for ensuring drug safety and advancing drug development, a topic that has garnered significant research interest. While existing methods have made considerable progress, approaches relying solely on known DDIs face a key challenge when applied to drugs with limited data (e.g., novel and few-shot drugs): insufficient exploration of the space of unlabeled pairwise drugs. To address these issues, we innovatively introduce S2VM, a Selfsupervised Visual pretraining framework for pair-wise Molecules, to fully fuse structural representations and explore the space of drug pairs for DDI prediction. S2VM incorporates the explicit structure and correlations of visual molecules, such as the positional relationships and connectivity between functional substructures. Specifically, we blend the visual fragments of drug pairs into a unified input for joint encoding and then recover molecule-specific visual information for each drug individually.

Mole Fractions indicates mole fractions availability. Arrhenius relationship indicates if the task can be modeled using the Arrhenius equation.

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein design from textual descriptions, yet struggle with structural plausibility. Inspired by classical protein design methods that leverage natural protein structures, we explore whether incorporating fragments from natural proteins can enhance foldability in generative models. Our empirical results show that even random incorporation of fragments improves foldability. Building on this insight, we introduce PRODVA, a novel protein design approach that integrates a text encoder for functional descriptions, a protein language model for designing proteins, and a fragment encoder to dynamically retrieve protein fragments based on textual functional descriptions. Experimental results demonstrate that our approach effectively designs protein sequences that are both functionally aligned and structurally plausible. Compared to state-of-the-art models, PRODVA achieves comparable function alignment using less than 0.04% of the training data, while designing significantly more well-folded proteins, with the proportion of proteins having pLDDT above 70 increasing by 7.38% and those with PAE below 10 increasing by 9.62%. 1

Transformer-based language models (LMs) have achieved widespread empirical success, but their theoretical expressive power remains only partially understood. In this work, we analyze a restricted idealization of fixed-precision transformers with strict future masking, soft attention, and no positional encodings. We establish that this class of models is exactly as expressive as a specific fragment of linear temporal logic that contains only a single temporal operator: the $\texttt{past}$ operator. We further connect this fragment to established classes in formal language theory, automata theory, and algebra, yielding a unified framework for understanding transformer expressivity under this idealization. Finally, we present empirical results that align closely with our theory: transformers trained on languages within their characterized expressive capacity generalize reliably across sequence lengths, while they consistently fail to generalize on languages beyond it.

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein design from textual descriptions, yet struggle with structural plausibility. Inspired by classical protein design methods that leverage natural protein structures, we explore whether incorporating fragments from natural proteins can enhance foldability in generative models. Our empirical results show that even random incorporation of fragments improves foldability. Building on this insight, we introduce ProDVa, a novel protein design approach that integrates a text encoder for functional descriptions, a protein language model for designing proteins, and a fragment encoder to dynamically retrieve protein fragments based on textual functional descriptions. Experimental results demonstrate that our approach effectively designs protein sequences that are both functionally aligned and structurally plausible. Compared to state-of-the-art models, ProDVa achieves comparable function alignment using less than 0.04% of the training data, while designing significantly more well-folded proteins, with the proportion of proteins having pLDDT above 70 increasing by 7.38% and those with PAE below 10 increasing by 9.62%.

A.1 Additional experimental results We further introduce our additional experiments in this section. In our main article, we compared our model FREED with baseline models REINVENT and MORLD. For fairer comparison of quality scores, we also performed multi-objective optimization of REINVENT and MORLD on both quality score (pharmacochemical filter score) and docking score as follows. Table 1 in the main text shows that such an implicit method is not enough to achieve nearly perfect filter scores as our model did. Also, as shown in Table 1 REINVENT showed deteriorated performance when jointly trained with filter scores, in terms of hit ratio and top 5% scores, implying that multiobjective optimization is more difficult than explicitly constrained optimization. Such a result was consistent for all three targets. The two baseline models REINVENT and MORLD that are jointly trained to maximize filter scores are noted as REINVENT w/ filter and MORLD w/ filter.

The vocabulary Vconstructed by Algorithm 1 exhibits the following advantageous properties. Prior to the proof, we first present a clear observation of the created vocabulary V: Proposition A.2. Given any F,F V, for any their instances arising on an arbitrary molecule during the extraction process, either they are not spatially intersected F F =, or they contain each other: F F or F F. Now we prove each claim in the above theorem. We prove it by contradiction. If it is the former case, then Fi1 should be firstly extracted and then merged with other fragments to yield Fi2 which means i1 < i2, conflicting with the assumption.