Investigating targets for neuropharmacological intervention by molecular dynamics simulations

Biochem Soc Trans. 2019 Jun 28;47(3):909-918. doi: 10.1042/BST20190048. Epub 2019 May 13.

Abstract

Medical research has identified over 500 brain disorders. Among these, there are still only very few neuropathologies whose causes are fully understood and, consequently, very few drugs whose mechanism of action is known. No FDA drug has been identified for major neurodegenerative diseases, such as Alzheimer's and Parkinson's. We still lack effective treatments and strategies for modulating progression or even early neurodegenerative disease onset diagnostic tools. A great support toward the highly needed identification of neuroactive drugs comes from computer simulation methods and, in particular, from molecular dynamics (MD). This provides insight into structure-function relationship of a target and predicts structure, dynamics and energetics of ligand/target complexes under biologically relevant conditions like temperature and physiological saline concentration. Here, we present examples of the predictive power of MD for neuroactive ligands/target complexes. This brief survey from our own research shows the usefulness of partnerships between academia and industry, and from joint efforts between experimental and theoretical groups.

Keywords: drug discovery and design; molecular dynamics; neuropathology.

Publication types

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

MeSH terms

  • Drug Discovery
  • Humans
  • Molecular Dynamics Simulation
  • Neurodegenerative Diseases / drug therapy*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Neuroprotective Agents