A New Multi-Objective Approach for Molecular Docking Based on RMSD and Binding Energy

Ligand-protein docking is an optimization problem based on predicting the position of a ligand with the lowest binding energy in the active site of the receptor. Molecular docking problems are traditionally tackled with single-objective, as well as with multi-objective approaches, to minimize the binding energy. In this paper, we propose a novel multi-objective formulation that considers: the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands and the binding (intermolecular) energy, as two objectives to evaluate the quality of the ligand-protein interactions. To determine the kind of Pareto front approximations that can be obtained, we have selected a set of representative multi-objective algorithms such as NSGA-II, SMPSO, GDE3, and MOEA/D. Their performances have been assessed by applying two main quality indicators intended to measure convergence and diversity of the fronts. In addition, a comparison with LGA, a reference single-objective evolutionary algorithm for molecular docking (AutoDock) is carried out. In general, SMPSO shows the best overall results in terms of energy and RMSD (value lower than 2A for successful docking results). This new multi-objective approach shows an improvement over the ligand-protein docking predictions that could be promising in in silico docking studies to select new anticancer compounds for therapeutic targets that are multidrug resistant.

Dynamic Multi-Objective Optimization With jMetal and Spark: a Case Study

Technologies for Big Data and Data Science are receiving increasing research interest nowadays. This paper introduces the prototyping architecture of a tool aimed to solve Big Data Optimization problems. Our tool combines the jMetal framework for multi-objective optimization with Apache Spark, a technology that is gaining momentum. In particular, we make use of the streaming facilities of Spark to feed an optimization problem with data from different sources. We demonstrate the use of our tool by solving a dynamic bi-objective instance of the Traveling Salesman Problem (TSP) based on near real-time traffic data from New York City, which is updated several times per minute. Our experiment shows that both jMetal and Spark can be integrated providing a software platform to deal with dynamic multi-optimization problems.

On multimodality of obnoxious faclity location models

Obnoxious single facility location models are models that have the aim to find the best location for an undesired facility. Undesired is usually expressed in relation to the so-called demand points that represent locations hindered by the facility. Because obnoxious facility location models as a rule are multimodal, the standard techniques of convex analysis used for locating desirable facilities in the plane may be trapped in local optima instead of the desired global optimum. It is assumed that having more optima coincides with being harder to solve. In this thesis the multimodality of obnoxious single facility location models is investigated in order to know which models are challenging problems in facility location problems and which are suitable for site selection. Selected for this are the obnoxious facility models that appear to be most important in literature. These are the maximin model, that maximizes the minimum distance from demand point to the obnoxious facility, the maxisum model, that maximizes the sum of distance from the demand points to the facility and the minisum model, that minimizes the sum of damage of the facility to the demand points. All models are measured with the Euclidean distances and some models also with the rectilinear distance metric. Furthermore a suitable algorithm is selected for testing multimodality. Of the tested algorithms in this thesis, Multistart is most appropriate. A small numerical experiment shows that Maximin models have on average the most optima, of which the model locating an obnoxious linesegment has the most. Maximin models have few optima and are thus not very hard to solve. From the Minisum models, the models that have the most optima are models that take wind into account. In general can be said that the generic models have less optima than the weighted versions. Models that are measured with the rectilinear norm do have more solutions than the same models measured with the Euclidean norm. This can be explained for the maximin models in the numerical example because the shape of the norm coincides with a bound of the feasible area, so not all solutions are different optima. The difference found in number of optima of the Maxisum and Minisum can not be explained by this phenomenon.

Phylogenetic inference's algorithms

Phylogenetic inference consist in the search of an evolutionary tree to explain the best way possible genealogical relationships of a set of species. Phylogenetic analysis has a large number of applications in areas such as biology, ecology, paleontology, etc. There are several criterias which has been defined in order to infer phylogenies, among which are the maximum parsimony and maximum likelihood. The first one tries to find the phylogenetic tree that minimizes the number of evolutionary steps needed to describe the evolutionary history among species, while the second tries to find the tree that has the highest probability of produce the observed data according to an evolutionary model. The search of a phylogenetic tree can be formulated as a multi-objective optimization problem, which aims to find trees which satisfy simultaneously (and as much as possible) both criteria of parsimony and likelihood. Due to the fact that these criteria are different there won't be a single optimal solution (a single tree), but a set of compromise solutions. The solutions of this set are called "Pareto Optimal". To find this solutions, evolutionary algorithms are being used with success nowadays.This algorithms are a family of techniques, which aren���t exact, inspired by the process of natural selection. They usually find great quality solutions in order to resolve convoluted optimization problems. The way this algorithms works is based on the handling of a set of trial solutions (trees in the phylogeny case) using operators, some of them exchanges information between solutions, simulating DNA crossing, and others apply aleatory modifications, simulating a mutation. The result of this algorithms is an approximation to the set of the ���Pareto Optimal��� which can be shown in a graph with in order that the expert in the problem (the biologist when we talk about inference) can choose the solution of the commitment which produces the higher interest. In the case of optimization multi-objective applied to phylogenetic inference, there is open source software tool, called MO-Phylogenetics, which is designed for the purpose of resolving inference problems with classic evolutionary algorithms and last generation algorithms. REFERENCES [1] C.A. Coello Coello, G.B. Lamont, D.A. van Veldhuizen. Evolutionary algorithms for solving multi-objective problems. Spring. Agosto 2007 [2] C. Zambrano-Vega, A.J. Nebro, J.F Aldana-Montes. MO-Phylogenetics: a phylogenetic inference software tool with multi-objective evolutionary metaheuristics. Methods in Ecology and Evolution. En prensa. Febrero 2016.