Chemistry Reference
In-Depth Information
of most programs currently still requires improvement. Some simulations
determine the binding energy between ligand and receptor using relevant
information of the complex (atomic radius, torsional angles, charge, Van der
Waals (VDW), intermolecular hydrogen bonds as well as hydrophobicity of the
contact force). Scoring functions, used to evaluate the results of docking
conformations, yield three-dimensional coordinates, total energies and additional
parameters.
It could be however advantageous to reduce the computation time, due to the very
large size of the search space of possible conformations, with high-performance
search methods. Different evaluations, benchmarks, validations, comparisons,
libraries, programs and procedures are discussed throughout this chapter.
The topics discussed in this review are structure and ligand-based docking, virtual
screening, homology-based, fragment-based models, consensus docking,
biosisosteric replacements, scaffold hopping, pharmacophore modeling, induced fit,
chemogenomic approaches, knowledge based drug discovery, binding affinity
prediction, scoring functions, entropic contributions, molecular dynamics, water and
solvent effects, quantum mechanics/molecular mechanics, simulation of free
energies, molecular fields and shape, binding site-based methods, inverse molecular
docking, chemical universe, protein docking, stem cells, virtual screening, workflow
pipelines, different types of ligands/targets/interactions, cloud, high performance and
grid computing, post-processing, chemical libraries, confidence and the future,
description of 50 docking/screening programs, recent evaluations/validations/
benchmarking and selected applications of various models to drug design.
The authors published, during the last decade, numerous papers using the
computer-aided drug design methods mentioned above and discussed in the
following sections. The protocols used include docking and screening with
proposals of new leads for diseases such as Cancer, Aids, Diabetes, Alzheimer,
Parkinson and other diseases [1-37].
HISTORICAL
It has been more than twenty-five years to the foundation of JCAMD in 1987.
Many papers have been subsequently published describing conformational
