Protein structures errors

Although comparative modeling is the most accurate modeling approach, it is limited by its absolute need for a related template structure. For more than half of the proteins and two-thirds of domains, a suitable template structure cannot be detected or is not yet known [9,11]. In those cases where no useful template is available, the ab initio methods are the only alternative. These methods are currently limited to small proteins and at best result only in coarse models with an RMSD error for the atoms that is greater than 4 A. However, one of the most impressive recent improvements in the field of protein structure modeling has occurred in ab initio prediction [155-157]. 

In general, the R factor is between 0.15 and 0.20 for a well-determined protein structure. The residual difference rarely is due to large errors in the model of the protein molecule, but rather it is an inevitable consequence of errors and imperfections in the data. These derive from various sources, including slight variations in conformation of the protein molecules and inaccurate corrections both for the presence of solvent and for differences in the orientation of the microcrystals from which the crystal is built. This means that the final model represents an average of molecules that are slightly different both in conformation and orientation, and not surprisingly the model never corresponds precisely to the actual crystal. 

Hooft RW, Vriend G, Sander C, Abola EE. 1996. Errors in protein structures. Nature 381(6580) 272. 

In practice, turns seen in X-ray diffraction elucidated protein structures often fail to satisfy such strict criteria. Both structural variation and measurement error can lead to nonideal geometries, and this complexity has given rise to a variety of working definitions. The most common strategy defines a chain site as a turn when the C (j) Ca(i+3) distance is less than 7 A and the residues involved are not in a helix. 

In the past decade ProSa has been used to address a variety of problems in protein structure research. A list of references to the relevant publications is provided at the ProSa website [14]. Originally the program was designed to spot errors and faulty parts in protein structures - whether the structures were determined by experiment or by modeling does not matter [9]. 

Having located the heavy atom(s) in the unit cell, the crystallographer can compute the structure factors FH for the heavy atoms alone, using Eq. (5.15). This calculation yields both the amplitudes and the phases of structure factors Fh, giving the vector quantities needed to solve Eq. (6.9) for the phases ahkl of protein structure factors Fp. This completes the information needed to compute a first electron-density map, using Eq. (6.7). This map requires improvement because these first phase estimates contain substantial errors. I will discuss improvement of phases and maps in Chapter 7. 

The text has been substantially revised, many new examples incorporated and errors corrected. A substantial new chapter dealing with supramolecular chemistry has been incorporated. Once again, a deliberate decision was made to try to limit references to the secondary rather than the primary literature. Where structural data have been presented, the use of the files of the Cambridge Crystallographic Data Centre and the Brookhaven Protein Structure Data Base are gratefully acknowledged. 

Thus, rather than trial-and-error development of functionality, it should be possible to design functionality based on the principles of protein structure and function and the specificities of the enzymes used for modification. Use of immobilized exo- and endopeptidases in such technology could be especially attractive for the reasons listed in Table I, particularly since problems associated with autolysis would be eliminated and the extent of proteolytic reactions could be controlled with some precision. 

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