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Article ID: 733 - Last Modified:

What procedure do I follow if I want to mutate amino acid residues?

You can mutate an amino acid residue by right-clicking on the residue in the Workspace and choosing Mutate → new-residue. If you want to keep the original structure, you can duplicate it in the Project Table, then mutate the duplicate structure. To find the residue in the Workspace, type CTRL+F to display the Find toolbar, choose Residue number from the option menu, and type the residue number in the text box (e.g. A:167), then click the N (next) button.

You can also use the Fragments tab of the Build panel to mutate residues. Choose Amino acids from the Fragments option menu, select Mutate, then choose the mutant and click on the residue to mutate in the Workspace.

If you want to mutate a residue to a nonstandard residue, you can do this by mutating to the corresponding standard residue, then building the additional fragments onto the mutated standard residue. There are a few modified residues available in the Fragments tab of the Build panel, which you can mutate to using the method above. Choose Modified amino acids from the Fragments option menu to make use of these residues.

After you have performed the mutation, you should check that the side chain is in a suitable conformation. If it is not, you can right-click on the residue and choose Rotamers, to choose from the common side-chain rotamers. Alternatively, you can manually adjust the side chain. To relax the structure around the mutation, choose the mutated residue and its neighbors, and press CTRL+M for a short minimization.

If you have prepared the original structure with the Protein Preparation Wizard, it is probably not necessary to do so again; however it could be important to optimize the H-bond network, and to run the restrained minimization.

If there is a substantial size difference between the original and the new residue, or the side chain is not oriented correctly, you might need to use a Prime side-chain prediction to find a good conformation for the new residue and its neighbors.

If you expect more substantial changes in the receptor or the ligand pose with the mutation, you might need to run IFD to generate some alternative receptor conformations and ligand binding modes.

Our Biologics Suite offers several tools for mutating residues and analyzing the mutated structures.

Keywords: Maestro, Glide

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