Introduction

The purpose of this tutorial is to demonstrate how to use the VMD plugins cispeptide and chirality together with AutoIMD to ensure proper structure of peptide bonds and correct stereochemistry of proteins and nucleic acids. The described plugins are designed to work with proteins and nucleic acids and understand atom names as used by the force fields CHARMM and AMBER as well as the standard PDB naming convention for non-hydrogen atoms.

WARNING: The current implementation of the chirality plugin does not support DNA yet.

The following points aim to motivate the necessity of the of the presented plugins:

• Structures from PDB may contain errors in stereochemistry and peptide bond configuration;
• Errors in peptide bond configuration can be introduced by modeling;
• Poor starting conditions, i.e. atoms being too close to each other, can generate huge forces during the initial optimization of the structure leading to errors in structure;
• Molecular dynamics (MD) protocols which apply forces on the molecule may generate forces large enough to introduce errors.

Since MD force fields are defined to support either type of chirality or peptide bond configuration, optimization of the structure will not correct introduced errors.

At his stage, we would like to give a brief outline of the strategy behind the described plugins. The general strategy to ensure correct peptide bond and stereochemical configuration consists of four steps.

1

Identify unusual configuration at chiral centers and peptide bonds All cis peptide bonds are regarded being unusual. In case of chiral centers, those are regarded unusual which occur less often in nature, e.g. D-form of amino acids.

2

Inspect the found irregularities Although it is possible to convert all peptide bonds and chirality centers into their ``usual'' configuration (this feature will be implemented in the future), it is safer to decide for each irregularity individually. First, different chiral forms of biomolecules and true cis peptide bonds are used in biology. Second, it is not always unambiguous how to correct an unusual configuration; this is especially the case for peptide bonds.

3

Correct the structure if necessary using structure optimization (and equilibration) The correcting happens in two steps. First one atom is moved to ``preset'' a proper configuration. In a second step an the structure is relaxed using an MD force field plus restraints enforcing the proper configuration.

4

If proceeding with further MD simulations, apply restraints to preserve chirality and peptide bond configuration This step may be necessary, if the molecular system is used in a simulation in which large forces may be applied, e.g., MDFF, TMD etc.