Reading the three-dimensional structure of a protein from its amino acid sequence

Abstract

While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learnt how to extract this information so as to predict the detailed, biological active, three-dimensional structure of a protein whose sequence is known. This situation is not particularly satisfactory, in keeping with the fact that while linear sequencing of the amino acids specifying a protein is relatively simple to carry out, the determination of the folded-native-conformation can only be done by an elaborate X-ray diffraction analysis performed on crystals of the protein or, if the protein is very small, by nuclear magnetic resonance techniques. Using insight obtained from lattice model simulations of the folding of small proteins (fewer than 100 residues), in particular of the fact that this phenomenon is essentially controlled by conserved contacts among strongly interacting amino acids, which also stabilize local elementary structures formed early in the folding process and leading to the (post-critical) folding core when they assemble together, we have worked out a successful strategy for reading the three-dimensional structure of a notional protein from its amino acid sequence.