Basic Workshop - Hands on Session 4

(Note: These tutorials are meant to provide illustrative examples of how to use the AMBER software suite to carry out simulations that can be run on a simple workstation in a reasonable period of time. They do not necessarily provide the optimal choice of parameters or methods for the particular application area.)
Copyright Ross Walker 2008

BASIC WORKSHOP
HANDS ON TUTORIAL 4

Using Antechamber to Create Leap Input Files for Simulating Sustiva
using the General Amber Force Field

By Ross Walker

In this tutorial we will make use of the Antechamber tools, which ship with AmberTools, in order to create an input file that can be read by Leap so that we can create prmtop and inpcrd files for simulations of organic molecules.

Antechamber is designed to be used with the "general AMBER force field (GAFF)". This force field has been specifically designed to cover most pharmaceutical molecules and is compatible with the traditional AMBER force fields in such a way that the two can be mixed during a simulation. Like the traditional AMBER force fields, GAFF uses a simple harmonic function form for bonds and angles but unlike the traditional protein and DNA orientated AMBER force fields the atom types used in GAFF are much more general such that they cover most of the organic chemical space. The current implementation of the GAFF force field consists of 33 basic atom types and 22 special atom types. The charge methods used can be HF/6-31G* RESP or AM1-BCC².

By design, GAFF, is a complete force field (so that missing parameters rarely occur), it covers almost all the organic chemical space that is made up of C, N, O, S, P, H, F, Cl, Br and I. Moreover, since GAFF is totally compatible with the AMBER macromolecular force fields it should prove to be an useful molecular mechanical tool for rational drug design. Especially in binding free energy calculations and molecular docking studies.

The Antechamber tool set is designed to allow the rapid generation of topology files for use with the AMBER simulation programs. This is useful in situations where you want to automatically screen a large number of compounds. Allowing antechamber to calculate charges and atom types automatically for us using GAFF allows it to be included in shell scripts that process a large number of compounds. However, as with any automated system it is not perfect and if you plan on focusing on a single system you should consider manually assigning atom types and carefully validating things. With Antechamber, one may solve the following problems:

Automatically identify bond and atom types
Judge atomic equivalence
Generate residue topology files
Find missing force field parameters and supply reasonable suggestions

Remember though that Antechamber is not a replacement for due diligence. You should always closely examine the atom types that Antechamber assigns and verify to yourself that the choices are reasonable. You should never use scientific software in a "Black Box" approach!

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