Prime User Manual - ISP

Prime User Manual
Chapter 7: Prime–Refinement
Chapter 7
Prime–Refinement is a module used to refine protein structures from the Maestro Workspace.
The methods can be applied to protein structures from any source, including one built using the
Prime–Structure Prediction workflow. It runs independently of Prime–SP from its own
Maestro panel, the Refinement panel. The Refinement panel offers the following refinement
protocols: loop refinement, side-chain prediction, minimization, and a single-point energy
calculation at the current geometry of the model structure.
In many cases, Prime–Refinement is used on protein structures from sources other than Prime,
but it can also be used with structures added to a project from the Build Structure step in the
Prime–SP module. A model structure built in the Build Structure step may require further
refinement. If there are insertions or deletions in the alignment between query and template, it
is recommended that you perform a loop refinement, since insertions and deletions are most
frequently found in loop regions. As another example, if you have added a water molecule to
the binding site of the protein, you can use Prime–Refinement on the composite entry.
Prime–Refinement can also refine structures with covalently bound ligands. The ligands can be
multiply connected, covalently bound to each other and to the protein. This capability allows
the refinement of proteins with phosphorylated residues or attached sugars, for example.
Prime–Refinement has an implicit membrane model, in which the membrane is modeled by a
slab of low dielectric constant in which the protein is immersed. The width of the slab and the
orientation of the protein with respect to the slab can be adjusted.
7.1 Preparing Structures for Refinement
Prime–Refinement has a great deal of flexibility in the types of structures it can handle, and can
fix many structural problems. For standard residues, Prime–Refinement can fix formal charges
and bond orders, and correct disparities between the sequence and the structure. For example,
if a residue has the coordinates of ALA but is called SER, the 3HB will be ignored and the OG
and HG added during refinement. The standard residues are the 20 canonical amino acids;
ACE and NMA; HOH; CYX (disulfide); and the acid/base variants ASH/AS1 (ASP), GLH/
GL1 (GLU), ARN (ARG), LYN (LYS), HIE/HIP/HID (HIS), CYT (CYS), SRO (SER), TYO
(TYR).
Prime–Refinement has certain conditions that must be met by the input structures for a job to
be run successfully. Some of these conditions only apply to covalently bound ligands.
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