Jian Ouyang

Bangchen Yin, Jian Ouyang, Zhen Fan et al.

Local curvature of potential energy surfaces is critical for predicting certain experimental observables of molecules and materials from first principles, yet it remains far beyond reach for complex systems. In this work, we introduce a Hessian-informed Machine Learning Interatomic Potential (Hi-MLIP) that captures such curvature reliably, thereby enabling accurate analysis of associated thermodynamic and kinetic phenomena. To make Hessian supervision practically viable, we develop a highly efficient training protocol, termed Hessian INformed Training (HINT), achieving two to four orders of magnitude reduction for the requirement of expensive Hessian labels. HINT integrates critical techniques, including Hessian pre-training, configuration sampling, curriculum learning and stochastic projection Hessian loss. Enabled by HINT, Hi-MLIP significantly improves transition-state search and brings Gibbs free-energy predictions close to chemical accuracy especially in data-scarce regimes. Our framework also enables accurate treatment of strongly anharmonic hydrides, reproducing phonon renormalization and superconducting critical temperatures in close agreement with experiment while bypassing the computational bottleneck of anharmonic calculations. These results establish a practical route to enhancing curvature awareness of machine learning interatomic potentials, bridging simulation and experimental observables across a wide range of systems.

Jian Ouyang, Arman T, Ge Jin

This paper investigates the impact of incorrect data on the performance and safety of large language models (LLMs), specifically gpt-4o, during supervised fine-tuning (SFT). Although LLMs become increasingly vital across broad domains like finance, coding, law, and health, fine-tuning on incorrect data can lead to "emergent misalignment," producing harmful or deceptive outputs unrelated to the intended task. We evaluate gpt-4o models fine-tuned with varying ratios (10\% to 90\% correct) of both obviously and subtly incorrect data across four domains: coding, finance, health, and legal. Our findings show that even modest amounts of incorrect data (10-25\%) dramatically degrade domain performance and not moral alignment. A clear threshold of at least 50\% correct data is needed for models to consistently recover strong performance, though they rarely match the robustness and safety of the base model, which exhibits near-perfect alignment and zero dangerous completions out-of-the-box. This research emphasizes that the cost of incorrect data is heavy, highlighting the critical need for extremely high-quality data curation or, alternatively, leveraging robust base models without unnecessary fine-tuning for high-stakes applications.

Jianda Yue, Tingting Li, Jian Ouyang et al.

Taste peptides have emerged as promising natural flavoring agents attributed to their unique organoleptic properties, high safety profile, and potential health benefits. However, the de novo identification of taste peptides derived from animal, plant, or microbial sources remains a time-consuming and resource-intensive process, significantly impeding their widespread application in the food industry. Here, we present TastePepAI, a comprehensive artificial intelligence framework for customized taste peptide design and safety assessment. As the key element of this framework, a loss-supervised adaptive variational autoencoder (LA-VAE) is implemented to efficiently optimizes the latent representation of sequences during training and facilitates the generation of target peptides with desired taste profiles. Notably, our model incorporates a novel taste-avoidance mechanism, allowing for selective flavor exclusion. Subsequently, our in-house developed toxicity prediction algorithm (SpepToxPred) is integrated in the framework to undergo rigorous safety evaluation of generated peptides. Using this integrated platform, we successfully identified 73 peptides exhibiting sweet, salty, and umami, significantly expanding the current repertoire of taste peptides. This work demonstrates the potential of TastePepAI in accelerating taste peptide discovery for food applications and provides a versatile framework adaptable to broader peptide engineering challenges.