dissertation代写片断:Glantamine, its target Acetylcholine

 Glantamine, its target Acetylcholinesterase (AChE) and interactions
Contents

1, Introduction
    

2

2, Ligand - Galantamine (GNT)
    

2

2.1, Structural description
    

2

2.2, MM2 energy minimization
    

3

2.3, Drug likeness assessment
    

3

3, Acetylcholinesterase(AChE) (PDB 1W6R)
    

4

3.1, Primary structural information
    

4

3.2, Secondary Structural Information
    

5

3.3 Three Dimensional structure
    

6

4, Protein-ligand interactions
    

9

4.1, General view of interactions with in GNT-AchE complex
    

9

4.2,Comments on the fit of ligand into binding site
    

12

5, Conclusion
    

12

6, References
    

12

 
1, Introduction

Galantamine (GNT) (2D structure showed in Fig 1) is a tertiary alkaloid extracted from several species of Amarylidacae, discovered more than 52 years ago, it has been tested in various neurological applications and has been proved to be a potent reversible inhibitor to AChE. Details of this compound are provided from different perspectives in this part.
2, Ligand - Galantamine (GNT)
2.1 Structural description

Fig 1: 2D structure of GNT

Table 1: Basic chemistry information of GNT (information gathered form ChemOffice 2004)

Common name
    

Galantamine (GNT)

Chemical Formula
    

C17H21NO3

CAS number
    

357-70-0

IUPAC Name
    

(4aS,6R,8aS)- 5,6,9,10,11,12- hexahydro- 3-methoxy- 11-methyl- 4aH- 1benzofuro3a,3,2-ef2benzazepin- 6-ol

Smiles string
    

HC@12CC@@H(O)C=CC@11CCN(C)CC3=CC=C(OC)C(O2)=C13

Chiral Atom Count
    

3
    

Chiral Atoms
    

C3 C41 C42

Number of rings
    

4
    

Bond Count
    

45

Log P
    

1.2
    

Aromatic Bond
    

6

MR
    

84.22cm3/mol
    

CMR
    

7.9778

Molar Refractivity
    

78.20 cm3/mol
    

Normal Boiling Point
    

817.71 K

Henry's Constant (H)
    

10.37
    

Freezing Point
    

542.75 K

Melting point
    

578.64 K
    

Critical temp
    

855.94 K

Critical Pressure
    

23.35 bar
    

Critical Volume
    

803.50 cm3/mol

Gibbs Energy
    

151.32 kJ/mol
    

Heat of Formation
    

-255.66kJ/mol
2.2, MM2 energy minimization

In order to get a more stable and low-energy conformation, which is more likely to present in interaction between GNT and target protein, we run a MM2 energy minimization and output shows that orientation of functional groups in GNT change significantly, which can be observed very obviously in Figure 2.

Figure 2, Sequence of pictures showing 3D structure and Connolly surface of GNT before (A, C) and after (B, D) MM2 energy minimization, GNT is rendered as a ball-and-stick model and the surface is rendered in transparent solid model. This view is generated by Chem3D Ultra.