Motivation: Molecular docking is a method for structure-based drug design and structural molecular biology, which attempts to predict the position and orientation of a small molecule (ligand) in relation to a protein (receptor) to produce a stable complex with a minimum binding energy. One of the most widely used software packages for this purpose is AutoDock, which incorporates three metaheuristic techniques. We propose the integration of AutoDock with jMetalCpp, an optimization framework, thereby providing both single- and multi-objective algorithms that can be used to effectively solve docking problems. Results: The resulting combination of AutoDock + jMetalCpp allows users of the former to easily use the metaheuristics provided by the latter. In this way, biologists have at their disposal a richer set of optimization techniques than those already provided in AutoDock. Moreover, designers of metaheuristic techniques can use molecular docking for case studies, which can lead to more efficient algorithms oriented to solving the target problems. Availability and implementation: jMetalCpp software adapted to AutoDock is freely available as a C++ source code at http://khaos.uma.es/AutodockjMetal/. Contact: jfam@lcc.uma.es Supplementary information: Supplementary data are available at Bioinformatics online.

Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II), speed modulation multi-objective particle swarm optimization (SMPSO), third evolution step of generalized differential evolution (GDE3), multi-objective evolutionary algorithm based on decomposition (MOEA/D) and S-metric evolutionary multi-objective optimization (SMS-EMOA). We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA) provided by the AutoDock tool). Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

The human Epidermal Growth Factor (EGFR) plays an important role in signaling pathways, such as cell proliferation and migration. Mutations like G719S, L858R, T790M, G719S/T790M or T790M/L858R can alter its conformation, and, therefore, drug responses from lung cancer patients. In this context, candidate drugs are being tested and in silico studies are necessary to know how these mutations affect the ligand binding site. This problem can be tackled by using a multi-objective approach applied to the molecular docking problem. According to the literature, few studies are related to the application of multi-objective approaches by minimizing two or more objectives in drug discovery. In this study, we have used four algorithms (NSGA-II, GDE3, SMPSO and MOEA/D) to minimize two objectives: the ligand–receptor intermolecular energy and the RMSD score. We have prepared a set of instances that includes the wild-type EGFR kinase domain and the same receptor with somatic mutations, and then we assessed the performance of the algorithms by applying a quality indicator to evaluate the convergence and diversity of the reference fronts. The MOEA/D algorithm yields the best solutions to these docking problems. The obtained solutions were analyzed, showing promising results to predict candidate EGFR inhibitors by using this multi-objective approach.

Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) has been designed as standard clinical terminology for annotating Electronic Health Records (EHRs). EHRs textual information is used to classify patients’ diseases into an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) category (usually by an expert). Improving the accuracy of classification is the main purpose of using ontologies and OWL representations at the core of classification systems. In the last few years some ontologies and OWL representations for representing ICD-10-CM categories have been developed. However, they were not designed to be the basis for an automatic classification tool nor do they model ICD-10-CM inclusion terms as Web Ontology Language (OWL) axioms, which enables automatic classification. In this context we have developed Dione, an OWL representation of ICD-10-CM. Dione is the first OWL representation of ICD-10-CM, which is logically consistent, whose axioms define the ICD-10-CM inclusion terms by means of a methodology based on SNOMED CT/ICD-10-CM mappings. The ICD-10-CM exclusions are handled with these mappings. Dione currently contains 391,669 classes, 391,720 entity annotation axioms and 11,795 owl:equivalentClass axioms which have been constructed using 104,646 relationships extracted from the SNOMED CT/ICD-10-CM and BioPortal mappings included in Dione using the owl:intersectionOf and the owl:someValuesFrom statements. The resulting OWL representation has been classified and its consistency tested with the ELK reasoner. We have also taken three clinical records from the Virgen de la Victoria Hospital (Málaga, Spain) which have been manually annotated using SNOMED CT. These annotations have been included as instances to be classified by the reasoner. The classified instances show that Dione could be a promising ICD-10-CM OWL representation to support the classification of patients’ diseases. Dione is a first step towards the automatic classification of patients’ diseases by using SNOMED CT annotations embedded in Electronic Health Records (EHRs). The purpose of Dione is to standardise and formalise a medical terminology, thereby enabling new kinds of tools and new sets of functionalities to be developed. This in turn assists health specialists by providing classified information from EHRs and enables the automatic annotation of patients’ diseases with ICD-10-CM codes.