[Chimera-users] modeling non-standard amino acids
meng at cgl.ucsf.edu
Tue Aug 14 11:20:00 PDT 2007
Chimera does not predict changes in a molecule's conformational
ensemble resulting from mutations or other chemical modifications.
For a very constrained structure, it might be possible to get a
reasonable result by simply making the modification (see Build
Structure in Chimera) and minimizing (Minimize Structure).
However, it sounds like your structure has several rotatable bonds,
so prediction is not straightforward. In that case, Chimera could be
used to build in the initial change, but then figuring out what will
happen to the molecule's conformational space is a different story,
especially in a solvated environment or in complex with another
molecule. Attempts to do this fall in to two main categories:
(1) based on inspection of how things look after the chemical change
(for example, now atoms are clashing, or conversely, a new hydrogen
bond is formed) the user applies his own chemical intuition as to
what the downstream effects could be (for example, local unfolding,
side chain rotates away, ligand no longer binds, etc.). This can be
aided by the Chimera tools FindHBond and Find Clashes/Contacts, and
you can rotate bonds interactively (see Adjust Torsions).
(2) more intensive calculations are performed with another program -
say molecular dynamics in solvent and possibly in complex with a
binding partner. This is also done with the unmodified structure.
Then the trajectories or conformational ensembles are compared. Or,
you could perform a free energy calculation perturbing one structure
to another. I don't have a specific example, but many published
papers describe similar work, looking at protein mutations or
comparing drug/ligand affinities. Chimera has tools for viewing and
analyzing conformational ensembles (see the MD Movie tool) but not
for calculating them in the first place.
I hope this helps,
Elaine C. Meng, Ph.D. meng at cgl.ucsf.edu
UCSF Computer Graphics Lab and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
More information about the Chimera-users