The joys and perils of flexible fitting.
While performing their functions, biological macromolecules often form large, dynamically changing macromolecular assemblies. Only a relatively small number of such assemblies have been accessible to the atomic-resolution techniques X-ray crystallography and NMR. Electron microscopy in conjunction with image reconstruction has become the preferred alternative for revealing the structures of such macromolecular complexes. However, for most assemblies the achievable resolution is too low to allow accurate atomic modeling directly from the data. Yet, useful models often can be obtained by fitting atomic models of individual components into a low-resolution reconstruction of the entire assembly. Several algorithms for achieving optimal fits in this context were developed recently, many allowing considerable degrees of flexibility to account for binding-induced conformational changes of the assembly components. This chapter describes the advantages and potential pitfalls of these methods and puts them into perspective with alternative approaches such as iterative modular fitting of rigid-body domains.
Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, 10901 N Torrey Pines Rd, La Jolla, CA, 92037, USA, niels@sanfordburnham.org.
Niels
N
Volkmann
D000445:Aldehyde Oxidoreductases / Q000737:chemistry; D000465:Algorithms; D018360:Crystallography, X-Ray; D005340:Fibrinogen / Q000737:chemistry; D005969:Glutamate Dehydrogenase / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007781:Lactoferrin / Q000737:chemistry; D008854:Microscopy, Electron; D015233:Models, Statistical; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009097:Multienzyme Complexes / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D012229:Rhinovirus / Q000737:chemistry; D038222:gamma-Crystallins / Q000737:chemistry
D007140:Immunoglobulin Fab Fragments; D009097:Multienzyme Complexes; D038222:gamma-Crystallins; D005340:Fibrinogen; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D005969:Glutamate Dehydrogenase; D007781:Lactoferrin