Title:In Silico Studies in Drug Research Against Neurodegenerative Diseases
Volume: 16
Issue: 6
Author(s): Farahnaz Rezaei Makhouri and Jahan B. Ghasemi*
Affiliation:
- Chemistry Department, Faculty of Sciences, University of Tehran, Tehran,Iran
Keywords:
Neurodegenerative diseases, cheminformatics, chemometrics, in silico drug discovery and design, virtual screening,
virtual docking, QSAR, MD.
Abstract: Background: Neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic
lateral sclerosis, Parkinson's disease (PD), spinal cerebellar ataxias, and spinal and bulbar muscular
atrophy are described by slow and selective degeneration of neurons and axons in the central
nervous system (CNS) and constitute one of the major challenges of modern medicine. Computeraided
or in silico drug design methods have matured into powerful tools for reducing the number of
ligands that should be screened in experimental assays.
Methods: In the present review, the authors provide a basic background about neurodegenerative
diseases and in silico techniques in the drug research. Furthermore, they review the various in silico
studies reported against various targets in neurodegenerative diseases, including homology modeling,
molecular docking, virtual high-throughput screening, quantitative structure activity relationship
(QSAR), hologram quantitative structure activity relationship (HQSAR), 3D pharmacophore
mapping, proteochemometrics modeling (PCM), fingerprints, fragment-based drug discovery,
Monte Carlo simulation, molecular dynamic (MD) simulation, quantum-mechanical methods for
drug design, support vector machines, and machine learning approaches.
Results: Detailed analysis of the recently reported case studies revealed that the majority of them
use a sequential combination of ligand and structure-based virtual screening techniques, with particular
focus on pharmacophore models and the docking approach.
Conclusion: Neurodegenerative diseases have a multifactorial pathoetiological origin, so scientists
have become persuaded that a multi-target therapeutic strategy aimed at the simultaneous targeting
of multiple proteins (and therefore etiologies) involved in the development of a disease is recommended
in future.
