Molecular Dynamics as a Tool for Virtual Ligand Screening

Methods Mol Biol. 2018:1762:145-178. doi: 10.1007/978-1-4939-7756-7_9.


Rational drug design is essential for new drugs to emerge, especially when the structure of a target protein or catalytic enzyme is known experimentally. To that purpose, high-throughput virtual ligand screening campaigns aim at discovering computationally new binding molecules or fragments to inhibit a particular protein interaction or biological activity. The virtual ligand screening process often relies on docking methods which allow predicting the binding of a molecule into a biological target structure with a correct conformation and the best possible affinity. The docking method itself is not sufficient as it suffers from several and crucial limitations (lack of protein flexibility information, no solvation effects, poor scoring functions, and unreliable molecular affinity estimation).At the interface of computer techniques and drug discovery, molecular dynamics (MD) allows introducing protein flexibility before or after a docking protocol, refining the structure of protein-drug complexes in the presence of water, ions and even in membrane-like environments, and ranking complexes with more accurate binding energy calculations. In this chapter we describe the up-to-date MD protocols that are mandatory supporting tools in the virtual ligand screening (VS) process. Using docking in combination with MD is one of the best computer-aided drug design protocols nowadays. It has proved its efficiency through many examples, described below.

Keywords: Affinity; Clustering; Docking; Drug design; Interaction energy; Molecular dynamics; Protein–ligand complex; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computational Biology / methods*
  • Drug Design
  • Drug Evaluation, Preclinical / methods*
  • Ligands
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry
  • Proteins / metabolism*


  • Ligands
  • Proteins