Generative Enzyme Design Guided by Functionally Important Sites and Small-Molecule Substrates

Enzymes are genetically encoded biocatalysts capable of accelerating chemical reactions. How can we automatically design functional enzymes? In this paper, we propose EnzyGen, an approach to learn a unified model to design enzymes across all functional families. Our key idea is to generate an enzyme's amino acid sequence and their three-dimensional (3D) coordinates based on functionally important sites and substrates corresponding to a desired catalytic function. These sites are automatically mined from enzyme databases. EnzyGen consists of a novel interleaving network of attention and neighborhood equivariant layers, which captures both long-range correlation in an entire protein sequence and local influence from nearest amino acids in 3D space. To learn the generative model, we devise a joint training objective, including a sequence generation loss, a position prediction loss and an enzyme-substrate interaction loss. We further construct EnzyBench, a dataset with 3157 enzyme families, covering all available enzymes within the protein data bank (PDB). Experimental results show that our EnzyGen consistently achieves the best performance across all 323 testing families, surpassing the best baseline by 10.79% in terms of substrate binding affinity. These findings demonstrate EnzyGen's superior capability in designing well-folded and effective enzymes binding to specific substrates with high affinities.

Generating Games via LLMs: An Investigation with Video Game Description Language

Recently, the emergence of large language models (LLMs) has unlocked new opportunities for procedural content generation. However, recent attempts mainly focus on level generation for specific games with defined game rules such as Super Mario Bros. and Zelda. This paper investigates the game generation via LLMs. Based on video game description language, this paper proposes an LLM-based framework to generate game rules and levels simultaneously. Experiments demonstrate how the framework works with prompts considering different combinations of context. Our findings extend the current applications of LLMs and offer new insights for generating new games in the area of procedural content generation.

Functional Geometry Guided Protein Sequence and Backbone Structure Co-Design

Proteins are macromolecules responsible for essential functions in almost all living organisms. Designing reasonable proteins with desired functions is crucial. A protein's sequence and structure are strongly correlated and they together determine its function. In this paper, we propose NAEPro, a model to jointly design Protein sequence and structure based on automatically detected functional sites. NAEPro is powered by an interleaving network of attention and equivariant layers, which can capture global correlation in a whole sequence and local influence from nearest amino acids in three dimensional (3D) space. Such an architecture facilitates effective yet economic message passing at two levels. We evaluate our model and several strong baselines on two protein datasets, $\beta$-lactamase and myoglobin. Experimental results show that our model consistently achieves the highest amino acid recovery rate, TM-score, and the lowest RMSD among all competitors. These findings prove the capability of our model to design protein sequences and structures that closely resemble their natural counterparts. Furthermore, in-depth analysis further confirms our model's ability to generate highly effective proteins capable of binding to their target metallocofactors. We provide code, data and models in Github.

Joint Design of Protein Sequence and Structure based on Motifs

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose GeoPro, a method to design protein backbone structure and sequence jointly. Our motivation is that protein sequence and its backbone structure constrain each other, and thus joint design of both can not only avoid nonfolding and misfolding but also produce more diverse candidates with desired functions. To this end, GeoPro is powered by an equivariant encoder for three-dimensional (3D) backbone structure and a protein sequence decoder guided by 3D geometry. Experimental results on two biologically significant metalloprotein datasets, including $\beta$-lactamases and myoglobins, show that our proposed GeoPro outperforms several strong baselines on most metrics. Remarkably, our method discovers novel $\beta$-lactamases and myoglobins which are not present in protein data bank (PDB) and UniProt. These proteins exhibit stable folding and active site environments reminiscent of those of natural proteins, demonstrating their excellent potential to be biologically functional.

MOSPC: MOS Prediction Based on Pairwise Comparison

As a subjective metric to evaluate the quality of synthesized speech, Mean opinion score~(MOS) usually requires multiple annotators to score the same speech. Such an annotation approach requires a lot of manpower and is also time-consuming. MOS prediction model for automatic evaluation can significantly reduce labor cost. In previous works, it is difficult to accurately rank the quality of speech when the MOS scores are close. However, in practical applications, it is more important to correctly rank the quality of synthesis systems or sentences than simply predicting MOS scores. Meanwhile, as each annotator scores multiple audios during annotation, the score is probably a relative value based on the first or the first few speech scores given by the annotator. Motivated by the above two points, we propose a general framework for MOS prediction based on pair comparison (MOSPC), and we utilize C-Mixup algorithm to enhance the generalization performance of MOSPC. The experiments on BVCC and VCC2018 show that our framework outperforms the baselines on most of the correlation coefficient metrics, especially on the metric KTAU related to quality ranking. And our framework also surpasses the strong baseline in ranking accuracy on each fine-grained segment. These results indicate that our framework contributes to improving the ranking accuracy of speech quality.

PolyVoice: Language Models for Speech to Speech Translation

We propose PolyVoice, a language model-based framework for speech-to-speech translation (S2ST) system. Our framework consists of two language models: a translation language model and a speech synthesis language model. We use discretized speech units, which are generated in a fully unsupervised way, and thus our framework can be used for unwritten languages. For the speech synthesis part, we adopt the existing VALL-E X approach and build a unit-based audio language model. This grants our framework the ability to preserve the voice characteristics and the speaking style of the original speech. We examine our system on Chinese $\rightarrow$ English and English $\rightarrow$ Spanish pairs. Experimental results show that our system can generate speech with high translation quality and audio quality. Speech samples are available at https://speechtranslation.github.io/polyvoice.

Game-based Platforms for Artificial Intelligence Research

Games have been the perfect test-beds for artificial intelligence research for the characteristics that widely exist in real-world scenarios. Learning and optimisation, decision making in dynamic and uncertain environments, game theory, planning and scheduling, design and education are common research areas shared between games and real-world problems. Numerous open-sourced games or game-based environments have been implemented for studying artificial intelligence. In addition to single- or multi-player, collaborative or adversarial games, there has also been growing interest in implementing platforms for creative design in recent years. Those platforms provide ideal benchmarks for exploring and comparing artificial intelligence ideas and techniques. This paper reviews the game-based platforms for artificial intelligence research, discusses the research trend induced by the evolution of those platforms, and gives an outlook.