Modeling with Alternate Locations in X‑ray Protein Structures

In many molecular
modeling applications, the standard procedure
is still to handle proteins as single, rigid structures. While the
importance of conformational flexibility is widely known, handling
it remains challenging. Even the crystal structure of a protein usually
contains variability exemplified in alternate side chain orientations
or backbone segments. This conformational variability is encoded in
PDB structure files by so-called alternate locations (AltLocs). Most
modeling approaches either ignore AltLocs or resolve them with simple
heuristics early on during structure import. We analyzed the occurrence
and usage of AltLocs in the PDB and developed an algorithm to automatically
handle AltLocs in PDB files enabling all structure-based methods using
rigid structures to take the alternative protein conformations described
by AltLocs into consideration. A respective software tool named AltLocEnumerator
can be used as a structure preprocessor to easily exploit AltLocs.
While the amount of data makes it difficult to show impact on a statistical
level, handling AltLocs has a substantial impact on a case-by-case
basis. We believe that the inspection and consideration of AltLocs
is a very valuable approach in many modeling scenarios.