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This paper presents DMP3 (Dynamic Multilayer Perceptron 3), a multilayer perceptron (MLP) constructive training method that constructs MLPs by incrementally adding network elements of varying complexity to the network. DMP3 differs from other MLP construction techniques in several important ways, and the motivation for these differences are given. Information gain rather than error minimization is used to guide the growth of the network, which increases the utility of newly added network elements and decreases the likelihood that a premature dead end in the growth of the network will occur. The generalization performance of DMP3 is compared with that of several other well-known machine learning and neural network learning algorithms on nine real world data sets. Simulation results show that DMP3 performs better (on average) than any of the other algorithms on the data sets tested. The main reasons for this result are discussed in detail. [ABSTRACT FROM AUTHOR]

Background: Conventional de novo drug design is costly and time consuming, making it accessible to only the best resourced research organizations. An emergent approach to new drug development is drug repurposing, in which compounds that have already gone through some level of clinical testing are examined for efficacy against diseases divergent than their original application. Repurposing of existing drugs circumvents the time and considerable cost of early stages of drug development, and can be accelerated by using software to screen existing chemical databases to identify suitable drug candidates. Results: Small-molecule Peptide-Influenced Drug Repurposing (SPIDR) was developed to identify small molecule drugs that target a specific receptor by exploring the conformational binding space of peptide ligands. SPIDR was tested using the potent and selective 16-amino acid peptide α-conotoxin MII ligand and the α3β2-nicotinic acetylcholine receptor (nAChR) isoform. SPIDR incorporates a genetic algorithm-based, heuristic search procedure, which was used to explore the ligand binding domain of the α3β2-nAChR isoform using a library consisting of 640,000 α-conotoxin MII peptide analogs. The peptides that exhibited the highest affinity for α3β2-nAChR were used as models for a small-molecule structure similarity search of the PubChem Compound database. SPIDR incorporates the SimSearcher utility, which generates shape distribution signatures of molecules and employs multi-level K-means clustering to insure fast database queries. SPIDR identified non-peptide drugs with estimated binding affinities nearly double that of the native α-conotoxin MII peptide. Conclusions: SPIDR has been generalized and integrated into DockoMatic v 2.1. This software contains an intuitive graphical interface for peptide mutant screening workflow and facilitates mapping, clustering, and searching of local molecular databases, making DockoMatic a valuable tool for researchers in drug design and repurposing. [ABSTRACT FROM AUTHOR]