**Amalia Stefaniu**

**1**

compounds.

**Chapter 1**

Drug Design

*Amalia Stefaniu*

Introductory Chapter: Molecular

Techniques to Achieve Rational

Docking and Molecular Dynamics

Molecular docking and molecular mechanics simulations are important approaches to achieve a rational drug design or a chemical process modeling. It goes to deep molecular insights as structures and mechanisms helping researchers to characterize various conformations and molecular interactions in terms of energy and binding affinities, giving the possibility to search among dozens, hundreds of real or imaginary compounds, the most suitable for a precise, well-defined purpose. The biochemical purpose derives from the chosen macromolecular target, protein, or enzyme. Starting from a known substance with a known mechanism of action and biological activity, we can imagine other related compounds as drug candidates with better efficacy and fewer side effects. These in silico methods help us to identify and select among large compound libraries the most suitable therapeutic agent before even starting its chemical synthesis. That can be called virtual chemistry before reaction tube. It is very convenient, reducing

The purpose of this book project is to clearly explain the principles of molecular docking and molecular dynamics, with examples of algorithms and procedures proposed by different software programs for small molecule-protein or protein-protein

Molecular docking studies provide us an overview of type of interactions occurring in ligand (small molecule)-protein or protein-protein complexes and rank the

The concept of molecular recognition of ligand at the protein/enzyme active site, classically named "lock and key," has been extended at "hand and glove," considering the protein flexibility and reciprocal adaptability between the receptor and ligand [1]. Molecular dynamics simulations explore extrinsic surface and bulk properties of various forms of pharmaceutically active molecules to aid the selection of a successful candidate. It involves accurate evaluation of binding pathways, kinetics, and

Both these computer-aided drug design (CADD) methods lead to ligand identification and optimization, favoring rapid development of pharmaceutical

Different software algorithms use various approaches such as rigid protein or flexible protein, rigid receptor, soft receptor, flexible side chains, induced fit, or

the consumption of chemical reagents, preclinical, clinical trials, and time.

complexes of medical or materials sciences interest.

candidate poses by their affinity scoring function.

thermodynamics of ligands in different solvents.

multiple structure algorithms [2].

**1. Molecular docking approaches and challenges**

National Institute for Chemical - Pharmaceutical Research and Development – ICCF Bucharest, Department of Pharmaceutical Biotechnologies, Laboratory of Molecular Design and Molecular Docking, Bucharest, Romania
