COMPUTATIONAL IN SILICO LIGAND DOCKING EXPERIMENT LAB REPORT

STUDENT NAME

INSTITUTION NAME

COURSE NAME

DUE DATE

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Table of Contents

1. INTRODUCTION...................................................................................................................... 3

2. METHODOLOGY......................................................................................................................4

3. RESULTS.................................................................................................................................. 5

4. DISCUSSION.......................................................................................................................... 10

5. REFERENCES......................................................................................................................... 11

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Table of figures
Figure 1: Adrenaline 2D ligand....................................................................................................................6
Figure 2: Adrenaline 3D Ligand....................................................................................................................7
Figure 3: Docking Site [-1.5, 0.7, 13.1].........................................................................................................8
Figure 4: Docking site [-3.5, -1.3, -18.9]......................................................................................................9
Figure 5: Ligand docking results................................................................................................................10

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 1. INTRODUCTION

Ligand docking represents a computational approach employed in molecular biology and the

field of drug development. This method involves the prediction and analysis of binding

interactions between a small molecule, referred to as the ligand, and a target receptor, typically

a biomolecule such as a protein. The primary objective of ligand docking is to anticipate the

ligand's position and manner of binding to the receptor, providing insights into the nature and

strength of these binding interactions. This process contributes to a better understanding of the

molecular interplay between ligands and receptors.

This laboratory report centers on investigating ligand-receptor interactions through

computational techniques, encompassing both experimental (wet) and computational (dry)

laboratory conditions. The chosen ligand, adrenaline, hold significant relevance in the fields of

pharmacology and physiology. The DEEPSITE online server is employed to predict binding

pockets on receptor surfaces.

Utilizing adrenaline as the medication of interest and considering the amino acids surrounding a

binding site suitable for pharmaceutical docking, Galaxy7TM is utilized to conduct ligand

docking simulations. The primary aim is to identify potential binding configurations, a process

essential for understanding the pharmacological aspects of the interaction (Lee & Seok, 2016).

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 2. METHODOLOGY
A pre-made GPCR was used to create a three-dimensional adrenaline structure using the

molecular modeling program DEEPSITE. The orthosteric binding pocket was the largest

predicted pocket.

The binding pockets on receptor surfaces as well as the potential locations of binding pockets

within proteins were found using the DEEPSITE online resource. The amino acids that

surrounded the binding site were noted and identified.

Next, a drawing of the adrenaline ligand was created using Molview. These pockets were found

to be suitable for ligand docking tests using the Galaxy7TM online docking server. The receptor

was selected for docking based on data from the literature regarding the ligand's known

binding target. Molecular docking simulations were used to examine possible interactions and

binding conformations.

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 3. RESULTS

Figure 1: Adrenaline 2D ligand

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Figure 2: Adrenaline 3D Ligand

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Binding pockets (DEEPSITE)

Binding pocket 1

Figure 3: Docking Site [-1.5, 0.7, 13.1]

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Binding pocket 2

Figure 4: Docking site [-3.5, -1.3, -18.9]

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Figure 5: Ligand docking results

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 4. DISCUSSION
After the ligand docking was performed by the Galaxy Web server, the amino acids leucine,

valine, serine, isoleucine, threonine, lysine, and tyrosine were observed to play distinct roles in

creating a stable and specific environment for the ligand-receptor interaction, showcasing the

intricate molecular mechanisms involved in such biological processes. The following was

observed from the docking:

Serine, Isoleucine, and Threonine for Hydrogen Bonding: Serine, isoleucine, and threonine are

involved in enhancing stability through hydrogen bonding interactions. Hydrogen bonds are

important forces in molecular recognition and binding, contributing to the overall stability of

the ligand-receptor complex.

Tyrosine Controlling Ligand Orientation: Tyrosine is a factor controlling the orientation of the

ligand. The specific arrangement and orientation of molecules are critical for their functional

roles. Tyrosine in the binding pocket suggests its involvement in determining how the ligand

interacts with the receptor.

Leucine and Valine for Hydrophobic Environment: Leucine and valine contribute to creating a

favorable hydrophobic environment around bound adrenaline. Hydrophobic interactions play a

crucial role in stabilizing molecular structures in aqueous environments, such as those found

within biological systems.

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Lysine for Ionic Connections and Improved Selectivity: Lysine is involved in ionic connections,

which can enhance the specificity of the ligand-receptor interaction. Ionic interactions involve

charged particles and can contribute to the strength and selectivity of molecular binding.

The binding pocket is a specific region on the receptor where the ligand binds, and the presence

of these amino acids in this pocket indicates their direct involvement in the molecular

interactions.

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 5. REFERENCES
Lee, G. R., & Seok, C. (2016). Galaxy7TM: flexible GPCR–ligand docking by structure refinement.

Nucleic Acids Research, 44(W1), W502–W506.

Shen, C., Ding, J., Wang, Z., Cao, D., Ding, X., & Hou, T. (2020). From machine learning to deep

learning: Advances in scoring functions for protein–ligand docking. Wiley

Interdisciplinary Reviews: Computational Molecular Science, 10(1), e1429.

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