Application of MM-PBSA Methods in Virtual Screening

Giulio Poli, Carlotta Granchi, Flavio Rizzolio, Tiziano Tuccinardi

Research output: Contribution to journalReview articlepeer-review

Abstract

Computer-aided drug design techniques are today largely applied in medicinal chemistry. In particular, receptor-based virtual screening (VS) studies, in which molecular docking represents the gold standard in silico approach, constitute a powerful strategy for identifying novel hit compounds active against the desired target receptor. Nevertheless, the need for improving the ability of docking in discriminating true active ligands from inactive compounds, thus boosting VS hit rates, is still pressing. In this context, the use of binding free energy evaluation approaches can represent a profitable tool for rescoring ligand-protein complexes predicted by docking based on more reliable estimations of ligand-protein binding affinities than those obtained with simple scoring functions. In the present review, we focused our attention on the Molecular Mechanics-Poisson Boltzman Surface Area (MM-PBSA) method for the calculation of binding free energies and its application in VS studies. We provided examples of successful applications of this method in VS campaigns and evaluation studies in which the reliability of this approach has been assessed, thus providing useful guidelines for employing this approach in VS.

Original languageEnglish
Article number1971
Number of pages19
JournalMolecules
Volume25
Issue number8
DOIs
Publication statusPublished - Apr 23 2020

Keywords

  • Binding Sites
  • Drug Design
  • Ligands
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Protein Binding
  • Structure-Activity Relationship

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