Desmond Tutorial

3 Preparing Proteins with
Missing Residues or Side Chains
Overview
Most protein structures in the PDB database have missing residues or side chains with
missing atoms, mainly as a result of unresolved electron density. The Protein Preparation
Wizard does not address these issues, and so more work needs to be performed on the
model to prepare it for simulation. In many cases, the missing atoms must be filled in. In
other cases, you might have a complete experimental structure of a protein available, but
you want to simulate a mutant.
Although the Edit menu provides tools which can be used to fill in missing parts of a protein
structure, or replace one amino acid side chain with another for generating a mutant,
manually filling in entire residues—or even just a side chain—can be an extremely challenging
task that requires a lot of hands‐on experience with Maestro. Maestro offers a tool
called Prime that can be used to automatically build a three‐dimensional model of a complete
amino acid sequence. Note, however, that you need a license from Schrödinger, LLC
to use Prime. Of course, other tools outside the Maestro environment can also be used to
fill in missing residues or side chains.
Running Prime
While Prime is typically used as a three‐dimensional structure prediction tool because of
its comparative modeling and sophisticated ab‐initio loop prediction, it can also be
ʹfooledʹ into filling in missing residues and side chains in an incomplete protein structure,
and building a three‐dimensional model of a complete amino acid sequence. This section
explains the protein preparation aspects of using Prime.
September 2008 D. E. Shaw Research 29