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THE IMPACT OF LOCAL ACCURACY IN PROTEIN AND RNA STRUCTURES: VALIDATION AS AN ACTIVE TOOL
INTRODUCTION
The enormous wealth of macromolecular structure data already available and the even greater wealth soon to come—from structural genomics, from the push for atomic-resolution structures, and from the push to solve much larger biological complexes, often including nucleic acids as well as proteins—provides a treasure trove of functional, interactional, and evolutionary data that change the idea how one can do biology. To make an effective use of this great resource, however, it is important, among other things, to take into account the very large spread of accuracy in those data. Relatively low-resolution structures can be among the most valuable ones if they are of critical molecules or of large and complex cellular machinery. These structures show overall fold and relative positioning of their interacting parts and they often illuminate function in surprising ways, but one should not expect to learn from them fine details in an active or allosteric site or the critical local differences that determine specificity for molecular interactions. Cryoelectron microscopy techniques are developing rapidly and are especially good at characterizing movements in large complexes. In combination with crystal structures of the components, models with full atomic coordinates can be built; those show overall positioning well, but the interface details ...
