Yu Wang

Yu Wang, Chao Pang, Yuzhe Wang et al.

Leveraging artificial intelligence for automatic retrosynthesis speeds up organic pathway planning in digital laboratories. However, existing deep learning approaches are unexplainable, like "black box" with few insights, notably limiting their applications in real retrosynthesis scenarios. Here, we propose MechRetro, a chemical-mechanism-driven graph learning framework for interpretable retrosynthetic prediction and pathway planning, which learns several retrosynthetic actions to simulate a reverse reaction via elaborate self-adaptive joint learning. By integrating chemical knowledge as prior information, we design a novel Graph Transformer architecture to adaptively learn discriminative and chemically meaningful molecule representations, highlighting the strong capacity in molecule feature representation learning. We demonstrate that MechRetro outperforms the state-of-the-art approaches for retrosynthetic prediction with a large margin on large-scale benchmark datasets. Extending MechRetro to the multi-step retrosynthesis analysis, we identify efficient synthetic routes via an interpretable reasoning mechanism, leading to a better understanding in the realm of knowledgeable synthetic chemists. We also showcase that MechRetro discovers a novel pathway for protokylol, along with energy scores for uncertainty assessment, broadening the applicability for practical scenarios. Overall, we expect MechRetro to provide meaningful insights for high-throughput automated organic synthesis in drug discovery.

Zelai Xu, Yancheng Liang, Chao Yu et al.

Self-play (SP) is a popular multi-agent reinforcement learning (MARL) framework for solving competitive games, where each agent optimizes policy by treating others as part of the environment. Despite the empirical successes, the theoretical properties of SP-based methods are limited to two-player zero-sum games. However, for mixed cooperative-competitive games where agents on the same team need to cooperate with each other, we can show a simple counter-example where SP-based methods cannot converge to a global Nash equilibrium (NE) with high probability. Alternatively, Policy-Space Response Oracles (PSRO) is an iterative framework for learning NE, where the best responses w.r.t. previous policies are learned in each iteration. PSRO can be directly extended to mixed cooperative-competitive settings by jointly learning team best responses with all convergence properties unchanged. However, PSRO requires repeatedly training joint policies from scratch till convergence, which makes it hard to scale to complex games. In this work, we develop a novel algorithm, Fictitious Cross-Play (FXP), which inherits the benefits from both frameworks. FXP simultaneously trains an SP-based main policy and a counter population of best response policies. The main policy is trained by fictitious self-play and cross-play against the counter population, while the counter policies are trained as the best responses to the main policy's past versions. We validate our method in matrix games and show that FXP converges to global NEs while SP methods fail. We also conduct experiments in a gridworld domain, where FXP achieves higher Elo ratings and lower exploitabilities than baselines, and a more challenging football game, where FXP defeats SOTA models with over 94% win rate.