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| Title: | Conservation and prediction of solvent accessibility in protein families |
| Author: | Burkhard Rost & Chris Sander |
| Quote: | Proteins, 20, 216-226 (1994) |
Predicting three-dimensional (3D) protein structure alone from sequence in general is currently an insurmountable task. As intermediate step, a much simpler task has been pursued extensively: prediction of a projection of 3D structure onto 1D strings of secondary structure. Here, we present an analysis of another 1D projection of 3D structure: the relative solvent accessibility of a residue. We show that solvent accessibility is less conserved in 3D families than secondary structure: the average correlation of relative solvent accessibility between 3D homologues is only 0.66. This value provides an effective practical upper limit for the accuracy of predicting accessibility from sequence. We introduce a neural network system that predicts relative solvent accessibility (projected onto 10 discrete states) using evolutionary profiles of amino acid substitutions derived from multiple sequence alignments. Evaluated in a cross-validation test on 126 unique proteins, the correlation between predicted and observed relative accessibility is 0.54. For a ternary (buried, intermediate, exposed) description of relative accessibility the fraction of correctly predicted residue states is about 58%. In absolute terms, this accuracy appears poor, but given the relatively low conservation of accessibility in 3D families (correlation 0.66), the network system is not far from optimal performance. Prediction is best for buried residues, e.g. 86% of the completely buried sites are correctly predicted as having 0% relative accessibility.