Abstract
BackgroundThe knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties. Experimental methods are too slow for structure investigation on a large scale, while computational prediction methods offer alternatives that are continuously being improved. The international Comparative Assessment of Structure Prediction (CASP), an "a posteriori" evaluation of the quality of theoretical models when the experimental structure becomes available, demonstrates that predictions can be successful as well as unsuccessful, and this suggests the necessity for evaluations able to discard "a priori" the wrong models.ResultsWe analyzed different structural properties of globular proteins for experimentally solved proteins belonging to the four different structural classes: "mainly alpha", "mainly beta", "alpha/beta" and "alpha+beta". The properties were found to be linearly correlated to protein molecular weight, but with some differences among the four classes. These results were applied to develop an evaluation test of theoretical models based on the expected globular properties of proteins. To verify the success of our test, we applied it to several protein models submitted to the sixth edition of CASP. The best theoretical models, as judged by CASP assessors, were in agreement with the expected properties, while most of the low-quality models had not passed our evaluations.ConclusionThis study supports the need for careful checks to avoid the diffusion of incorrect structural models. Our test allows the evaluation of models in the absence of experimental reference structures, thereby preventing the diffusion of incorrect structural models and the formulation of incorrect functional hypotheses. It can be used to check the globularity of predicted models, and to supplement other methods already used to evaluate their quality.
Highlights
The knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties
This study supports the need for careful checks to avoid the diffusion of incorrect structural models
Protein set selection Protein structures, solved by NMR or X-Ray crystallography with resolution of 2.5 Å or better, were extracted from PDBselect [12]. These proteins were subdivided into four structural classes, i.e. "mainly alpha", "mainly beta", "alpha/beta" and "alpha+beta", on the bases of secondary structures assigned by DSSP program and of the SCOP database to classify the alpha-beta proteins as alpha+beta or alpha/beta [13,14,15]
Summary
The knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties. A basic difference between experimental and computational approaches to solve the 3D structure of proteins is that X-ray or NMR protocols start from high protein concentration conditions, while "ab initio" predictive methods run on a single protein molecule. This means that most predictive methods can not take into account the strong influence of environment on the globular structure of the protein. At least to evaluate the quality of the predictions, it is necessary to know whether the structural properties typical of globular proteins are retained by theoretical models
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