How to build a small molecule

 

1 Introduction
2 What's you need
3 The molecule to build
4 Building the molecule
5 Structure optimization
6 Conformational search

 

1 Introduction

This tutorial explains how to build a small molecule (e.g. a ligand) using the 3D molecular editor included in VEGA ZZ and how to perform a systematic conformational search (grid scan) in order to find the best conformer.

 

2 What you need

 

3 The molecule to build

Imagine to want to build the imipramine using the 3D molecular editor:


Imipramine

The editor is based on fragments databases containing building blocks that can be combined each other to complete a more complex structure. For this reason, you must cut the molecule in less complex fragments that will be assembled as indicated in the following scheme:

Excluding initially the heteroatoms, the system can be fragmented in a tricyclic system (Dibenzo[a,d]cycloheptane), in a n-butyl chain and in two methyl groups.

 

4 Building the molecule

The hydrogen will be deleted. Click the Done button to close the window.

Hydrogen to click

Click the Done button to close the window.

 

5 Structure optimization

In this section will be explained how to perform a conjugate gradient minimization in order to optimize the rough 3D structure.

 

6 Conformational search

In order to find a reasonable lowest energy conformation, it will be explained how to perform the conformational search of the built molecule. The flexible torsions (dihedrals) will be systematically rotated by an angle value (grid scan) and each conformation will be optimized  in order to find the best minimum.