This study introduces Purrfessor, an innovative AI chatbot designed to provide personalized dietary guidance through interactive, multimodal engagement. Leveraging the Large Language-and-Vision Assistant (LLaVA) model fine-tuned with food and nutrition data and a human-in-the-loop approach, Purrfessor integrates visual meal analysis with contextual advice to enhance user experience and engagement. We conducted two studies to evaluate the chatbot's performance and user experience: (a) simulation assessments and human validation were conducted to examine the performance of the fine-tuned model; (b) a 2 (Profile: Bot vs. Pet) by 3 (Model: GPT-4 vs. LLaVA vs. Fine-tuned LLaVA) experiment revealed that Purrfessor significantly enhanced users' perceptions of care ($\beta = 1.59$, $p = 0.04$) and interest ($\beta = 2.26$, $p = 0.01$) compared to the GPT-4 bot. Additionally, user interviews highlighted the importance of interaction design details, emphasizing the need for responsiveness, personalization, and guidance to improve user engagement.

The development of large language models and multi-modal models has enabled the appealing idea of generating novel molecules from text descriptions. Generative modeling would shift the paradigm from relying on large-scale chemical screening to find molecules with desired properties to directly generating those molecules. However, multi-modal models combining text and molecules are often trained from scratch, without leveraging existing high-quality pretrained models. That approach consumes more computational resources and prohibits model scaling. In contrast, we propose a lightweight adapter-based strategy named Chemical Language Model Linker (ChemLML). ChemLML blends the two single domain models and obtains conditional molecular generation from text descriptions while still operating in the specialized embedding spaces of the molecular domain. ChemLML can tailor diverse pretrained text models for molecule generation by training relatively few adapter parameters. We find that the choice of molecular representation used within ChemLML, SMILES versus SELFIES, has a strong influence on conditional molecular generation performance. SMILES is often preferable despite not guaranteeing valid molecules. We raise issues in using the large PubChem dataset of molecules and their associated descriptions for evaluating molecule generation and provide a filtered version of the dataset as a generation test set. To demonstrate how ChemLML could be used in practice, we generate candidate protein inhibitors and use docking to assess their quality.

Recent advances in protein language models have catalyzed significant progress in peptide sequence representation. Despite extensive exploration in this field, pre-trained models tailored for peptide-specific needs remain largely unaddressed due to the difficulty in capturing the complex and sometimes unstable structures of peptides. This study introduces a novel multi-view contrastive learning framework PepHarmony for the sequence-based peptide encoding task. PepHarmony innovatively combines both sequence- and structure-level information into a sequence-level encoding module through contrastive learning. We carefully select datasets from the Protein Data Bank (PDB) and AlphaFold database to encompass a broad spectrum of peptide sequences and structures. The experimental data highlights PepHarmony's exceptional capability in capturing the intricate relationship between peptide sequences and structures compared with the baseline and fine-tuned models. The robustness of our model is confirmed through extensive ablation studies, which emphasize the crucial roles of contrastive loss and strategic data sorting in enhancing predictive performance. The proposed PepHarmony framework serves as a notable contribution to peptide representations, and offers valuable insights for future applications in peptide drug discovery and peptide engineering. We have made all the source code utilized in this study publicly accessible via GitHub at https://github.com/zhangruochi/PepHarmony or http://www.healthinformaticslab.org/supp/.

Prompt recently have become an effective linguistic tool on utilizing the pre-trained language models. However, in few-shot scenarios, subtle changes of prompt's design always make the result widely different, and the prompt design is also easy to overfit the current limited samples. To alleviate this, we explore how to utilize suitable contrastive samples and multiple contrastive learning methods to realize a more robust prompt's representation. Therefore, the contrastive prompt model ConsPrompt combining with prompt encoding network, contrastive sampling modules, and contrastive scoring modules are introduced to realize differential contrastive learning. Our results exhibit the state-of-the-art performance in different few-shot settings, and the ablation experiments also certificate the effectiveness in utilizing multi-degree contrastive learning in prompt-based fine-tuning process.

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential evolutionary knowledge from the universe of natural protein sequences, to acquire an immediate capability to design preferable protein sequences for given folds. We conduct a structural surgery on pLMs, where a lightweight structural adapter is implanted into pLMs and endows it with structural awareness. During inference, iterative refinement is performed to effectively optimize the generated protein sequences. Experiments show that LM-Design improves the state-of-the-art results by a large margin, leading to up to 4% to 12% accuracy gains in sequence recovery (e.g., 55.65%/56.63% on CATH 4.2/4.3 single-chain benchmarks, and >60% when designing protein complexes). We provide extensive and in-depth analyses, which verify that LM-Design can (1) indeed leverage both structural and sequential knowledge to accurately handle structurally non-deterministic regions, (2) benefit from scaling data and model size, and (3) generalize to other proteins (e.g., antibodies and de novo proteins)