Multi-objective Metaheuristics for a Flexible Ligand-Macromolecule Docking Problem in Computational Biology

  • Esteban López CamachoEmail author
  • María Jesús García-Godoy
  • Javier Del Ser
  • Antonio J. Nebro
  • José F. Aldana-Montes
Conference paper
Part of the Studies in Computational Intelligence book series (SCI, volume 798)


The problem of molecular docking focuses on minimizing the binding energy of a complex composed by a ligand and a receptor. In this paper, we propose a new approach based on the joint optimization of three conflicting objectives: \(E_{inter}\) that relates to the ligand-receptor affinity, the \(E_{intra}\) characterizing the ligand deformity and the RMSD score (Root Mean Square Deviation), which measures the difference of atomic distances between the co-crystallized ligand and the computed ligand. In order to deal with this multi-objective problem, three different metaheuristic solvers (SMPSO, MOEA/D and MPSO/D) are used to evolve a numerical representation of the ligand’s conformation. An experimental benchmark is designed to shed light on the comparative performance of these multi-objective heuristics, comprising a set of HIV-proteases/inhibitors complexes where flexibility was applied. The obtained results are promising, and pave the way towards embracing the proposed algorithms for practical multi-criteria in the docking problem.


Molecular docking Multi-objective optimization Flexibility modeling SMPSO MOEA/D MPSO/D 



This work has been partially supported by the proyect grants TIN2014-58304 y TIN2017-86049-R (Ministerio de Economía, Industria y Competividad) and P12-TIC-1519 (Plan Andaluz de Investigación, Desarrollo e Innovación). Javier Del Ser would also like to thank the Basque Government for its support through the EMAITEK Funding Program.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Esteban López Camacho
    • 1
    Email author
  • María Jesús García-Godoy
    • 1
  • Javier Del Ser
    • 2
  • Antonio J. Nebro
    • 1
  • José F. Aldana-Montes
    • 1
  1. 1.Departamento de Lenguajes y Ciencias de la ComputaciónUniversity of MálagaMálagaSpain
  2. 2.TECNALIA, Univ. of the Basque Country (UPV/EHU) and Basque Center for Applied Mathematics (BCAM)BizkaiaSpain

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