Metadynamics Simulations Rationalise the Conformational Effects Induced by N-Methylation of RGD Cyclic Hexapeptides

Chemistry. 2015 Sep 28;21(40):14165-70. doi: 10.1002/chem.201501196. Epub 2015 Aug 6.

Abstract

We combined metadynamics, docking and molecular mechanics/generalised born surface area (MM/GBSA) re-scoring methods to investigate the impact of single and multiple N-methylation on a set of RGD cyclopeptides displaying different affinity for integrin αIIbβ3. We rationalised the conformational effects induced by N-methylation and its interplay with receptor affinity, obtaining good agreement with experimental data. This approach can be exploited before entering time-consuming and expensive synthesis and binding experiments.

Keywords: docking; integrin; metadynamics; methylation; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Methylation
  • Molecular Conformation
  • Molecular Dynamics Simulation
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism

Substances

  • Ligands
  • Peptides, Cyclic
  • Platelet Glycoprotein GPIIb-IIIa Complex