Rui Yan

Qizhi Pei, Kaiyuan Gao, Lijun Wu et al.

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this challenge, with sampling-based and regression-based methods emerging as two prominent approaches. However, these methods have notable limitations. Sampling-based methods often suffer from low efficiency due to the need for generating multiple candidate structures for selection. On the other hand, regression-based methods offer fast predictions but may experience decreased accuracy. Additionally, the variation in protein sizes often requires external modules for selecting suitable binding pockets, further impacting efficiency. In this work, we propose $\mathbf{FABind}$, an end-to-end model that combines pocket prediction and docking to achieve accurate and fast protein-ligand binding. $\mathbf{FABind}$ incorporates a unique ligand-informed pocket prediction module, which is also leveraged for docking pose estimation. The model further enhances the docking process by incrementally integrating the predicted pocket to optimize protein-ligand binding, reducing discrepancies between training and inference. Through extensive experiments on benchmark datasets, our proposed $\mathbf{FABind}$ demonstrates strong advantages in terms of effectiveness and efficiency compared to existing methods. Our code is available at https://github.com/QizhiPei/FABind

Shufang Xie, Rui Yan, Junliang Guo et al.

Retrosynthesis, which predicts the reactants of a given target molecule, is an essential task for drug discovery. In recent years, the machine learing based retrosynthesis methods have achieved promising results. In this work, we introduce RetroKNN, a local reaction template retrieval method to further boost the performance of template-based systems with non-parametric retrieval. We first build an atom-template store and a bond-template store that contain the local templates in the training data, then retrieve from these templates with a k-nearest-neighbor (KNN) search during inference. The retrieved templates are combined with neural network predictions as the final output. Furthermore, we propose a lightweight adapter to adjust the weights when combing neural network and KNN predictions conditioned on the hidden representation and the retrieved templates. We conduct comprehensive experiments on two widely used benchmarks, the USPTO-50K and USPTO-MIT. Especially for the top-1 accuracy, we improved 7.1% on the USPTO-50K dataset and 12.0% on the USPTO-MIT dataset. These results demonstrate the effectiveness of our method.

Rui Yan, Zongying Shi, Yisheng Zhong

This paper considers a subspace guarding game in high-dimensional space which consists of a play subspace and a target subspace. Two faster defenders cooperate to protect the target subspace by capturing an attacker which strives to enter the target subspace from the play subspace without being captured. A closed-form solution is provided from the perspectives of kind and degree. Contributions of the work include the use of the attack subspace (AS) method to construct the barrier, by which the game winner can be perfectly predicted before the game starts. In addition to this inclusion, with the priori information about the game result, a critical payoff function is designed when the defenders can win the game. Then, the optimal strategy for each player is explicitly reformulated as a saddle-point equilibrium. Finally, we apply these theoretical results to a half-space guarding game in three-dimensional space. Since the whole achieved developments are analytical, they require a little memory without computational burden and allow for real-time updates, beyond the capacity of traditional Hamilton-Jacobi-Isaacs method. It is worth noting that this is the first time in the current work to consider the target guarding games for arbitrary high-dimensional space, and in a fully analytical form.

Xiaoxi Sun, Jinpeng Li, Yan Zhong et al.

The advent of large language models (LLMs) has facilitated the development of natural language text generation. It also poses unprecedented challenges, with content hallucination emerging as a significant concern. Existing solutions often involve expensive and complex interventions during the training process. Moreover, some approaches emphasize problem disassembly while neglecting the crucial validation process, leading to performance degradation or limited applications. To overcome these limitations, we propose a Markov Chain-based multi-agent debate verification framework to enhance hallucination detection accuracy in concise claims. Our method integrates the fact-checking process, including claim detection, evidence retrieval, and multi-agent verification. In the verification stage, we deploy multiple agents through flexible Markov Chain-based debates to validate individual claims, ensuring meticulous verification outcomes. Experimental results across three generative tasks demonstrate that our approach achieves significant improvements over baselines.

Rui Yan, Gabriel Santos, Gethin Norman et al.

Neuro-symbolic approaches to artificial intelligence, which combine neural networks with classical symbolic techniques, are growing in prominence, necessitating formal approaches to reason about their correctness. We propose a novel modelling formalism called neuro-symbolic concurrent stochastic games (NS-CSGs), which comprise two probabilistic finite-state agents interacting in a shared continuous-state environment. Each agent observes the environment using a neural perception mechanism, which converts inputs such as images into symbolic percepts, and makes decisions symbolically. We focus on the class of NS-CSGs with Borel state spaces and prove the existence and measurability of the value function for zero-sum discounted cumulative rewards under piecewise-constant restrictions on the components of this class of models. To compute values and synthesise strategies, we present, for the first time, practical value iteration (VI) and policy iteration (PI) algorithms to solve this new subclass of continuous-state CSGs. These require a finite decomposition of the environment induced by the neural perception mechanisms of the agents and rely on finite abstract representations of value functions and strategies closed under VI or PI. First, we introduce a Borel measurable piecewise-constant (B-PWC) representation of value functions, extend minimax backups to this representation and propose a value iteration algorithm called B-PWC VI. Second, we introduce two novel representations for the value functions and strategies, constant-piecewise-linear (CON-PWL) and constant-piecewise-constant (CON-PWC) respectively, and propose Minimax-action-free PI by extending a recent PI method based on alternating player choices for finite state spaces to Borel state spaces, which does not require normal-form games to be solved.

Rui Yan, Xiaoming Duan, Zongying Shi et al.

This paper introduces two metrics (cycle-based and memory-based metrics), grounded on a dynamical game-theoretic solution concept called sink equilibrium, for the evaluation, ranking, and computation of policies in multi-agent learning. We adopt strict best response dynamics (SBRD) to model selfish behaviors at a meta-level for multi-agent reinforcement learning. Our approach can deal with dynamical cyclical behaviors (unlike approaches based on Nash equilibria and Elo ratings), and is more compatible with single-agent reinforcement learning than alpha-rank which relies on weakly better responses. We first consider settings where the difference between largest and second largest underlying metric has a known lower bound. With this knowledge we propose a class of perturbed SBRD with the following property: only policies with maximum metric are observed with nonzero probability for a broad class of stochastic games with finite memory. We then consider settings where the lower bound for the difference is unknown. For this setting, we propose a class of perturbed SBRD such that the metrics of the policies observed with nonzero probability differ from the optimal by any given tolerance. The proposed perturbed SBRD addresses the opponent-induced non-stationarity by fixing the strategies of others for the learning agent, and uses empirical game-theoretic analysis to estimate payoffs for each strategy profile obtained due to the perturbation.