When planning a mutation to test some hypothesis, one
crucial question is whether the new side chain is compatible
with the existing structure; only if it is compatible can
the interpretation of mutational results be straightforward.
This paper presents a simple way of using the sensitive
geometry of all-atom contacts (including hydrogens) to
answer that question. The interactive MAGE/PROBE system
lets the biologist explore conformational space for the
mutant side chain, with an interactively updated kinemage
display of its all-atom contacts to the original structure.
The Autobondrot function in PROBE systematically explores
that same conformational space, outputting contact scores
at each point, which are then contoured and displayed.
These procedures are applied here in two types of test
cases, with known mutant structures. In ricin A chain,
the ability of a neighboring glutamate to rescue activity
of an active-site mutant is modeled successfully. In T4
lysozyme, six mutations to Leu are analyzed within the
wild-type background structure, and their Autobondrot score
maps correctly predict whether or not their surroundings
must shift significantly in the actual mutant structures;
interactive examination of contacts for the conformations
involved explains which clashes are relieved by the motions.
These programs are easy to use, are available free for
UNIX or Microsoft Windows operating systems, and should
be of significant help in choosing good mutation experiments
or in understanding puzzling results.