Molecular Docking in Drug Discovery

In last few years the Computer Aided Drug Design and Discovery is many success rates. In academics and many pharmaceutical industries for drug lead discovery they adopt the Computational Drug Design. The modern era of drug discovery and development structural information play an important role. For visualization of 3D-structure of molecule different docking program are developed. The docking score is analysed by using computer-based drug design software. It is structure based virtual screening method for the orientation, conformation, position into a structure of target molecule. Ligand and Protein docking is new concept. Molecular docking method complication is optimization of lead molecule, biological pathway evaluation and de Novo drug design.


INTRODUCTION
The Suitable orientation of ligand molecule overs the receptor molecule to build a stable complex is called as molecular docking [1][2][3][4][5][6][7]. This orientation utilized for the binding affinity prediction and strength of connection of ligand and protein by using scoring function. The drug receptor interaction predicts the affinity and activity of molecule [8][9][10][11][12][13][14][15][16][17]. It plays vital role in drug design and drug discovery. It is minimized overall free energy of system. New drug discovery and development is very challenging task. With the help of In-Silico method new drug discovery occurs [18][19][20][21][22][23][24][25][26][27]. For the rapid gaining of drug discovery process the computer-based drug design should be used. It is useful in structural biology of molecule and computational drug design [28][29][30][31][32][33][34][35]. It is used to anticipate the 3-Dimensional structure of molecule. With the help of scoring function currently rank candidates docking for large libraries compound perform the virtual screening [36-42].

COMPUTER AIDED DRUG DESIGN
It is computer-based technique used in the computational chemistry to discover, enhance or study of drug and related biologically active molecule is called as (CADD) Computer Aided Drug Design.
1. It is most useful in new drug design. 2. It provides knowledge about the chemical and biological properties of ligands and targets. 3. It is used to find and improve novel drug.
4. Discovery of in-silico filters for prediction of undesirable properties like poor activity and poor Pharmacokinetic and Toxicity of drug molecule. 5. It is used for the optimization of novel drug targets. CADD is being used to find hits 6. By using chemical scaffolds to find out novel Virtual screening is applied for new drug molecules.

LIGAND-BASED DRUG DESIGN
Ligand-based exploits the knowledge of known active and inactive molecules for chemical similarity searches or quantitative structure activity relation (QSAR). Ligand-based, is ideal where the 3D structure of the target proteins are not available.
Structural-Based Computer Aided Drug Design: Steps includes: (1) For docking Preparation of the target protein and compound library, (2) Determining a Proper binding pose for each compound, and (3) Ranking the docked structures of molecules.
To predicts the orientations or conformations of a receptor-ligand complex by using the Molecular docking and it is a structural based computer simulation procedure and used to predict the binding affinity between the molecules in the complex. To predicts the orientations or conformations of a ligand complex by using the Molecular and it is a structural based computer simulation procedure and used to predict the binding affinity between the molecules in the

TYPES OF MOLECULAR DOCKING
The experimentation method determines the binding modes and number of configurations creates. For docking analysis, the Monte Carlo method, fragment and genetic based, systemic searches is applied.
In this docking the receptor and ligand molecule both are fixed. Docking is In this docking the ligand and the receptor both are movable. It is conformationally flexible. Each rotation the mation surface cell occupancy is calculated. After that the most binding affinity is corresponding to the binding score. The best binders are best scoring ligands. It can be knowledge and molecular mechanics based. Docking Scoring is play important role in designing of drug: a) Knowledge-based scoring function the statistics of the observed inter contact frequencies in a large database of the crystal structure of protein complexes. Molecular interactions close to the maximum frequency of interactions in the data-base will have a high binding affinity [80][81][82][83][84][85]. A molecular interaction with a low binding affinity in data base will have a low frequency of interaction. b) Energy component scoring method based on the mathematical assumption that change in free energy upon binding of a ligand to a protein target (DG bind) is the sum of the free energy for ligand interaction, ligand-protein and solvent interaction, conformational changes in the ligand and protein and the motion in the ligand and protein target during complex formation [86-90].

MOLECULAR DOCKING MECHANICS STEPS
In In-Silico method studied the intermolecular interaction between 2 drug molecules. The protein receptor is Macromolecule. It acted as an inhibitor. The following steps involved in docking process are as. based scoring function uses the statistics of the observed inter-atomic contact frequencies in a large database of the crystal structure of protein-ligand complexes. Molecular interactions close to the maximum frequency of interactions in base will have a high binding . A molecular interaction with a low binding affinity in data base will have a low frequency of interaction.
Energy component scoring method is based on the mathematical assumption that change in free energy upon binding of rotein target (DG bind) is the sum of the free energy for ligand-protein protein and solvent interaction, conformational changes in the ligand and protein and the motion in the ligand and protein target during complex

MOLECULAR DOCKING MECHANICS
Silico method studied the intermolecular interaction between 2 drug molecules. The protein receptor is Macromolecule. It acted as an inhibitor. The following steps involved in docking Step II -Ligand Preparation: By using different databases such as ZINC, Pub Chem Ligands molecule can be downloaded. It can be draw in Chem sketch tool in mol file. Then utilized LIPINSKY'S RULE OF 5 for this ligand molecule. It is used for the drug like and unlike molecules. It increases the high chance of success rate and decrease the failure  Step III-Grid Generation: In this site, rotatable group, excluded volumes, constraints kept constant. The num operations performed (crossover, migration, mutation) is the key parameter in determining. Binding Cavity Prediction are to be done.

TYPES OF MOLECULAR DOCKING
Step IV -Prediction of Active site: site of protein molecule should be predicted. after that Preparation of protein, the water molecules and hetero atoms if present they are removed from cavity.
Step V-Docking: Ligand and protein interactions are analyzed. Best docking score should be selected.

FLEXIBLE OR INDUCED FIT
Step I-Protein Prepration Step II-Prepration of ligand Step III-Grid Generation Step IV-Active site prediction Step 4-Docking

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.