Search techniques, such as Monte Carlo Tree Search (MCTS) and Proof-Number Search (PNS), are effective in playing and solving games. However, the understanding of their performance in industrial applications is still limited. We investigate MCTS and Depth-First Proof-Number (DFPN) Search, a PNS variant, in the domain of Retrosynthetic Analysis (RA). We find that DFPN's strengths, that justify its success in games, have limited value in RA, and that an enhanced MCTS variant by Segler et al. significantly outperforms DFPN. We address this disadvantage of DFPN in RA with a novel approach to combine DFPN with Heuristic Edge Initialization. Our new search algorithm DFPN-E outperforms the enhanced MCTS in search time by a factor of 3 on average, with comparable success rates.

Proof-Number Search is a best-first search algorithm with many successful applications, especially in game solving. As large-scale computing clusters become increasingly accessible, parallelization is a natural way to accelerate computation. However, existing parallel versions of Proof-Number Search are known to scale poorly on many CPU cores. Using two parallelized levels and shared information among workers, we present the first massively parallel version of Proof-Number Search that scales efficiently even on a large number of CPUs. We apply our solver, enhanced with Grundy numbers for reducing game trees, to the Sprouts game, a case study motivated by the long-standing Sprouts Conjecture. Our solver achieves a significantly improved 332.9$\times$ speedup when run on 1024 cores, enabling it to outperform the state-of-the-art Sprouts solver GLOP by four orders of magnitude in runtime and to generate proofs 1,000$\times$ more complex. Despite exponential growth in game tree size, our solver verified the Sprouts Conjecture for 42 new positions, nearly doubling the number of known outcomes.

This paper presents Generalized Proof-Number Monte-Carlo Tree Search: a generalization of recently proposed combinations of Proof-Number Search (PNS) with Monte-Carlo Tree Search (MCTS), which use (dis)proof numbers to bias UCB1-based Selection strategies towards parts of the search that are expected to be easily (dis)proven. We propose three core modifications of prior combinations of PNS with MCTS. First, we track proof numbers per player. This reduces code complexity in the sense that we no longer need disproof numbers, and generalizes the technique to be applicable to games with more than two players. Second, we propose and extensively evaluate different methods of using proof numbers to bias the selection strategy, achieving strong performance with strategies that are simpler to implement and compute. Third, we merge our technique with Score Bounded MCTS, enabling the algorithm to prove and leverage upper and lower bounds on scores - as opposed to only proving wins or not-wins. Experiments demonstrate substantial performance increases, reaching the range of 80% for 8 out of the 11 tested board games.

Image created using DALL-E with the prompt "Games, Chemistry, Artificial Intelligence". In modern pharmaceutical research, active ingredients are designed using a computer. Only in a second step, one determines, still away from the wet lab, whether these complex molecules can actually be synthesized. This is considered a true art among chemists as it is highly complex and requires a broad knowledge of chemical reactions. At the pharmaceutical company Bayer, one uses a time-intensive Artificial Neural Network (ANN) to predict which reactions could immediately produce the candidate at hand.

The production of any new medicine requires solutions to many planning problems. The most fundamental of these is determining the sequence of chemical reactions necessary to physically create the drug. Surprisingly, these organic syntheses can be modeled as branching paths in a discrete, fully-observable state space, making the construction of new medicines an application of heuristic search. We describe a model of organic chemistry that is amenable to traditional AI techniques from game tree search, regression, and automatic assembly sequencing. We demonstrate the applicability of AND/OR graph search by developing the first chemistry solver to use proof-number search. Finally, we construct a benchmark suite of organic synthesis problems collected from undergraduate organic chemistry exams, and we analyze our solvers performance both on this suite and in recreating the synthetic plan for a multibillion dollar drug.

Depth-first proof-number search (df-pn) is powerful AND/OR tree search to solve positions in games. However, df-pn has a notorious problem of infinite loops when applied to domains with repetitions. Df-pn(r) cures it by ignoring proof and disproof numbers that may lead to infinite loops. This paper points out that df-pn(r) has a serious issue of underestimating proof and disproof numbers, while it also suffers from the overestimation problem occurring in directed acyclic graph. It then presents two practical solutions to these problems. While bypassing infinite loops, the threshold controlling algorithm (TCA) solves the underestimation problem by increasing the thresholds of df-pn. The source node detection algorithm (SNDA) detects the cause of overestimation and modifies the computation of proof and disproof numbers. Both TCA and SNDA are implemented on top of df-pn to solve tsume-shogi (checkmating problem in Japanese chess). Results show that df-pn with TCA and SNDA is far superior to df-pn(r). Our tsume-shogi solver is able to solve several difficult positions previously unsolved by any other solvers.