**Author details**

*Molecular Docking and Molecular Dynamics*

ing a docking simulation.

receptor druggability [3].

Pharmaceutical applications

cytotoxicity).

in the docking software as \*.pdb or compatible file.

The steps for conducting molecular docking studies are:

• Ligand preparation consists in generation, optimization, and analysis of its 3D structure. Among multiple conformers, the most stable, as lowest energy, can be used for docking simulations. An aspect to be considered is the fact that in physiological media, the ligand appears ionized. The effect of solvation due to the surrounded water molecules must be solved. The presence of active site water molecules influences the docking pose of the ligand and makes questionable the accuracy of the method [2]. Three-dimensional structures of small ligand molecules are available in virtual databases such as Cambridge Structural Database (CSD), Available Chemical Directory (ACD), MDL Drug

Data Report (MDDR), or National Cancer Institute Database (NCI).

• Receptor preparation. The use of a rigid target protein will conduct a single conformation of the receptor. Flexible protein involves different conformations to bind the ligand. Often the site water molecules are removed before perform-

Protein Data Bank (https://www.rcsb.org/) provides various solved 3D structures of protein, protein fragments, nucleic acids, and protein-ligand complexes. The assemblies are characterized by X-ray crystallography, nuclear magnetic resonance (NMR), infrared spectroscopy, and or/electron density and are available as PDB files format. This online tool allows us to explore and analyze the structures or to compare any protein in the PDB archive, including support for rigid-body and flexible alignments. Also, for simulation the optimized ligand structure must be imported and used

• Identify the binding site: This step plays a key role in structure-based drug design. It can be determined experimentally or computationally. Some software are created to identifying and analyzing binding sites and predicting

• Dock ligands: Different algorithms are used, fragment-based algorithms,

• Docking validation and results analysis: For validation, the software must reproduce the real binding site that was founded and characterized by X-ray crystallography or NMR techniques. To dock ligand similar derivative structures, the same binding site is used, and different conformation dues to rotations around flexible bond are performed for each new structure. The results conduct to predicting preferential binding orientation and the strength of binding affinity, interactions (type, strength, bond length); the conformations are ranked by mean of scoring functions [or root-mean-score deviation (RMSD)]. Furthermore, the stability of receptor-ligand complexes is assessed,

and ligand/pharmaceutical small compound druggability is evaluated.

• Exploring DNA binding properties of some malignant tumor chemotherapeutic agents [4–7] (to identify the DNA binding site, to predict interactions between potential therapeutic compound and DNA, to assess the stability of DNA-complexes, and to establish correlations between structure and

genetic algorithm, Monte Carlo algorithms, and molecular dynamics protocols.

**2**

Amalia Stefaniu National Institute for Chemical, Pharmaceutical Research and Development, Romania

\*Address all correspondence to: astefaniu@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
