Hi Daniel, 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). http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/editing/ editing.html http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/minimize/ minimize.html 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). http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/findhbond/ findhbond.html http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/findclash/ findclash.html http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/ structuremeas/structuremeas.html#adjust (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. http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/movie/ framemovie.html http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/tutorials/ ensembles2.html I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. meng@cgl.ucsf.edu UCSF Computer Graphics Lab and Babbitt Lab Department of Pharmaceutical Chemistry University of California, San Francisco http://www.cgl.ucsf.edu/home/meng/index.html