Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models within a single algorithmic category, cross-algorithm comparisons remain scarce. In this paper, to fill the gap, we establish a benchmark to evaluate the performance of sixteen models across these different algorithmic foundations by assessing the pharmaceutical properties of the generated molecules and their docking affinities with specified target proteins. We highlight the unique advantages of each algorithmic approach and offer recommendations for the design of future SBDD models. We emphasize that 1D/2D ligand-centric drug design methods can be used in SBDD by treating the docking function as a black-box oracle, which is typically neglected. The empirical results show that 1D/2D methods achieve competitive performance compared with 3D-based methods that use the 3D structure of the target protein explicitly. Also, AutoGrow4, a 2D molecular graph-based genetic algorithm, dominates SBDD in terms of optimization ability.

Molecule synthesis through machine learning is one of the fundamental problems in drug discovery. Current data-driven strategies employ one-step retrosynthesis models and search algorithms to predict synthetic routes in a top-bottom manner. Despite their effective performance, these strategies face limitations in the molecule synthetic route generation due to a greedy selection of the next molecule set without any lookahead. Furthermore, existing strategies cannot control the generation of synthetic routes based on possible criteria such as material costs, yields, and step count. In this work, we propose a general and principled framework via conditional residual energy-based models (EBMs), that focus on the quality of the entire synthetic route based on the specific criteria. By incorporating an additional energy-based function into our probabilistic model, our proposed algorithm can enhance the quality of the most probable synthetic routes (with higher probabilities) generated by various strategies in a plug-and-play fashion. Extensive experiments demonstrate that our framework can consistently boost performance across various strategies and outperforms previous state-of-the-art top-1 accuracy by a margin of 2.5%. Code is available at https://github.com/SongtaoLiu0823/CREBM.

Neural predictors are effective in boosting the time-consuming performance evaluation stage in neural architecture search (NAS), owing to their direct estimation of unseen architectures. Despite the effectiveness, training a powerful neural predictor with fewer annotated architectures remains a huge challenge. In this paper, we propose a context-aware neural predictor (CAP) which only needs a few annotated architectures for training based on the contextual information from the architectures. Specifically, the input architectures are encoded into graphs and the predictor infers the contextual structure around the nodes inside each graph. Then, enhanced by the proposed context-aware self-supervised task, the pre-trained predictor can obtain expressive and generalizable representations of architectures. Therefore, only a few annotated architectures are sufficient for training. Experimental results in different search spaces demonstrate the superior performance of CAP compared with state-of-the-art neural predictors. In particular, CAP can rank architectures precisely at the budget of only 172 annotated architectures in NAS-Bench-101. Moreover, CAP can help find promising architectures in both NAS-Bench-101 and DARTS search spaces on the CIFAR-10 dataset, serving as a useful navigator for NAS to explore the search space efficiently.

Partially Observable Markov Decision Processes (POMDPs) are powerful models for sequential decision making under transition and observation uncertainties. This paper studies the challenging yet important problem in POMDPs known as the (indefinite-horizon) Maximal Reachability Probability Problem (MRPP), where the goal is to maximize the probability of reaching some target states. This is also a core problem in model checking with logical specifications and is naturally undiscounted (discount factor is one). Inspired by the success of point-based methods developed for discounted problems, we study their extensions to MRPP. Specifically, we focus on trial-based heuristic search value iteration techniques and present a novel algorithm that leverages the strengths of these techniques for efficient exploration of the belief space (informed search via value bounds) while addressing their drawbacks in handling loops for indefinite-horizon problems. The algorithm produces policies with two-sided bounds on optimal reachability probabilities. We prove convergence to an optimal policy from below under certain conditions. Experimental evaluations on a suite of benchmarks show that our algorithm outperforms existing methods in almost all cases in both probability guarantees and computation time.

In this work, we introduce LazyBoE, a multi-query method for kinodynamic motion planning with forward propagation. This algorithm allows for the simultaneous exploration of a robot's state and control spaces, thereby enabling a wider suite of dynamic tasks in real-world applications. Our contributions are three-fold: i) a method for discretizing the state and control spaces to amortize planning times across multiple queries; ii) lazy approaches to collision checking and propagation of control sequences that decrease the cost of physics-based simulation; and iii) LazyBoE, a robust kinodynamic planner that leverages these two contributions to produce dynamically-feasible trajectories. The proposed framework not only reduces planning time but also increases success rate in comparison to previous approaches.

We propose adaptive, line search-free second-order methods with optimal rate of convergence for solving convex-concave min-max problems. By means of an adaptive step size, our algorithms feature a simple update rule that requires solving only one linear system per iteration, eliminating the need for line search or backtracking mechanisms. Specifically, we base our algorithms on the optimistic method and appropriately combine it with second-order information. Moreover, distinct from common adaptive schemes, we define the step size recursively as a function of the gradient norm and the prediction error in the optimistic update. We first analyze a variant where the step size requires knowledge of the Lipschitz constant of the Hessian. Under the additional assumption of Lipschitz continuous gradients, we further design a parameter-free version by tracking the Hessian Lipschitz constant locally and ensuring the iterates remain bounded. We also evaluate the practical performance of our algorithm by comparing it to existing second-order algorithms for minimax optimization.

In this paper, an improved method for VR user experience prediction is investigated by introducing a sparrow search algorithm and a random forest algorithm improved by an iterative local search-optimised sparrow search algorithm. The study firstly conducted a statistical analysis of the data, and then trained and tested using the traditional random forest model, the random forest model improved by the sparrow search algorithm, and the random forest algorithm improved based on the iterative local search-sparrow search algorithm, respectively. The results show that the traditional random forest model has a prediction accuracy of 93% on the training set but only 73.3% on the test set, which is poor in generalisation; whereas the model improved by the sparrow search algorithm has a prediction accuracy of 94% on the test set, which is improved compared with the traditional model. What is more noteworthy is that the improved model based on the iterative local search-sparrow search algorithm achieves 100% accuracy on both the training and test sets, which is significantly better than the other two methods. These research results provide new ideas and methods for VR user experience prediction, especially the improved model based on the iterative local search-sparrow search algorithm performs well and is able to more accurately predict and classify the user's VR experience. In the future, the application of this method in other fields can be further explored, and its effectiveness can be verified through real cases to promote the development of AI technology in the field of user experience.

We consider the resolution of learning problems involving $\ell_0$-regularization via Branch-and-Bound (BnB) algorithms. These methods explore regions of the feasible space of the problem and check whether they do not contain solutions through "pruning tests". In standard implementations, evaluating a pruning test requires to solve a convex optimization problem, which may result in computational bottlenecks. In this paper, we present an alternative to implement pruning tests for some generic family of $\ell_0$-regularized problems. Our proposed procedure allows the simultaneous assessment of several regions and can be embedded in standard BnB implementations with a negligible computational overhead. We show through numerical simulations that our pruning strategy can improve the solving time of BnB procedures by several orders of magnitude for typical problems encountered in machine-learning applications.

Subgroup-discovery methods allow users to obtain simple descriptions of interesting regions in a dataset. Using constraints in subgroup discovery can enhance interpretability even further. In this article, we focus on two types of constraints: First, we limit the number of features used in subgroup descriptions, making the latter sparse. Second, we propose the novel optimization problem of finding alternative subgroup descriptions, which cover a similar set of data objects as a given subgroup but use different features. We describe how to integrate both constraint types into heuristic subgroup-discovery methods. Further, we propose a novel Satisfiability Modulo Theories (SMT) formulation of subgroup discovery as a white-box optimization problem, which allows solver-based search for subgroups and is open to a variety of constraint types. Additionally, we prove that both constraint types lead to an NP-hard optimization problem. Finally, we employ 27 binary-classification datasets to compare heuristic and solver-based search for unconstrained and constrained subgroup discovery. We observe that heuristic search methods often yield high-quality subgroups within a short runtime, also in scenarios with constraints.

In this paper, we propose a novel algorithm for epistemic planning based on dynamic epistemic logic (DEL). The novelty is that we limit the depth of reasoning of the planning agent to an upper bound b, meaning that the planning agent can only reason about higher-order knowledge to at most (modal) depth b. The algorithm makes use of a novel type of canonical b-bisimulation contraction guaranteeing unique minimal models with respect to b-bisimulation. We show our depth-bounded planning algorithm to be sound. Additionally, we show it to be complete with respect to planning tasks having a solution within bound b of reasoning depth (and hence the iterative bound-deepening variant is complete in the standard sense). For bound b of reasoning depth, the algorithm is shown to be (b + 1)-EXPTIME complete, and furthermore fixed-parameter tractable in the number of agents and atoms. We present both a tree search and a graph search variant of the algorithm, and we benchmark an implementation of the tree search version against a baseline epistemic planner.