This article delves into the security control challenges posed by networked switched systems (NSSs) in the face of deception attacks and denial-of-service (DoS) attacks. It takes an active perspective and proposes an enhanced two-tier Stackelberg game approach to influence the actions of the deception attacker, controller, and DoS attacker. By formulating the cost functions for these three participants, it seeks to derive the optimal solution and the interplay between their respective optimal strategies. Meanwhile, two complicated situations are taken into account: The asynchronous behavior between the system and controller is caused by deception attacks tampering with switching signals; The open-loop operation of the system is caused by DoS attacks blocking the output of the controller. In the joint design of the two-tier multiattacker Stackelberg game approach and average dwell time technique, the system's mean square exponential stability is guaranteed while revealing the quantitative relationship between the deception attack, DoS attack, and asynchronous switching behaviors. Finally, a simulation result of a switched RLC circuit confirms the validity of the obtained active security control methodology.

SUMMARY: Molecular-similarity searches based on two-dimensional (2D) fingerprint and three-dimensional (3D) shape represent two widely used ligand-based virtual screening (VS) methods in computer-aided drug design. 2D fingerprint-based VS utilizes the binary fragment information on a known ligand, whereas 3D shape-based VS takes advantage of geometric information for predefined features from a 3D conformation. Given their different advantages, it would be desirable to hybridize 2D fingerprint and 3D shape molecular-similarity approaches in drug discovery. Here, we presented a general hybrid molecular-similarity protocol, referred to as HybridSim, obtained by combining the 2D fingerprint- and 3D shape-based similarity search methods and evaluated its performance on 595,036 actives and decoys for 40 pharmaceutically relevant targets available in the Directory of Useful Decoys Enhanced (DUD-E). Our results showed that HybridSim significantly improved the overall performance in 40 VS projects as compared with using only 2D fingerprint and 3D shape methods. Furthermore, HybridSim-VS, the first online platform using the proposed HybridSim method coupled with 17,839,945 screenable and purchasable compounds, was developed to provide large-scale and proficient VS capabilities to experts and nonexperts in the field. AVAILABILITY AND IMPLEMENTATION: HybridSim-VS web server is freely available at http://www.rcidm.org/HybridSim-VS/. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Evaluation of the capacity for separating actives from challenging decoys is a crucial metric of performance related to molecular docking or a virtual screening workflow. The Directory of Useful Decoys (DUD) and its enhanced version (DUD-E) provide a benchmark for molecular docking, although they only contain a limited set of decoys for limited targets. DecoyFinder was released to compensate the limitations of DUD or DUD-E for building target-specific decoy sets. However, desirable query template design, generation of multiple decoy sets of similar quality, and computational speed remain bottlenecks, particularly when the numbers of queried actives and retrieved decoys increases to hundreds or more. Here, we developed a program suite called RApid DEcoy Retriever (RADER) to facilitate the decoy-based assessment of virtual screening. This program adopts a novel database-management regime that supports rapid and large-scale retrieval of decoys, enables high portability of databases, and provides multifaceted options for designing initial query templates from a large number of active ligands and generating subtle decoy sets. RADER provides two operational modes: as a command-line tool and on a web server. Validation of the performance and efficiency of RADER was also conducted and is described. AVAILABILITY AND IMPLEMENTATION: RADER web server and a local version are freely available at http://rcidm.org/rader/ . CONTACT: [email protected] or [email protected] . SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.