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 that you want to build imipramine using the 3D molecular editor:

 

Imipramine 2D structure
Imipramine

 

 

The editor is based on fragment 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:

 

Imipramine fragments

 

Excluding initially the heteroatoms, the molecule 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 first building block

Atom to click

Hydrogen to remove

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

Butane hydrogen to click

Hydrogen to click

Carbon to click

Hydrogen to remove

Click Done to close the window.

Ammine hydrogen to click

Final 3D structure

 

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.