NMR and computational methods in the structural and dynamic characterization of ligand-receptor interactions

Adv Exp Med Biol. 2014:805:271-304. doi: 10.1007/978-3-319-02970-2_12.

Abstract

The recurrent failures in drug discovery campaigns, the asymmetry between the enormous financial investments and the relatively scarce results have fostered the development of strategies based on complementary methods. In this context in recent years the rigid lock-and-key binding concept had to be revisited in favour of a dynamic model of molecular recognition accounting for conformational changes of both the ligand and the receptor. The high level of complexity required by a dynamic description of the processes underlying molecular recognition requires a multidisciplinary investigation approach. In this perspective, the combination of nuclear magnetic resonance spectroscopy with molecular docking, conformational searches along with molecular dynamics simulations has given new insights into the dynamic mechanisms governing ligand receptor interactions, thus giving an enormous contribution to the identification and design of new and effective drugs. Herein a succinct overview on the applications of both NMR and computational methods to the structural and dynamic characterization of ligand-receptor interactions will be presented.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Binding Sites
  • Cell Line, Tumor
  • Drug Discovery*
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / chemistry*
  • Kinetics
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Monte Carlo Method
  • Oligopeptides / chemistry*
  • Protein Binding
  • Protein Conformation
  • Thermodynamics

Substances

  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • Ligands
  • Oligopeptides
  • arginyl-glycyl-aspartic acid