A critical view on conservative mutations.
By analysing the surface composition of a set of protein 3D structures, complemented with predicted surface compositional information for homologous proteins, we have found significant evidence for a layer composition of protein structures. In the innermost and outermost parts of proteins there is a net negative charge, while the middle has a net positive charge. In addition, our findings indicate that the concept of conservative mutation needs substantial revision, e.g. very different spatial preferences were found for glutamic acid and aspartic acid. The alanine screening often used in protein engineering projects involves the substitution of residues to alanine, based on the assumption that alanine is a "neutral" residue. However, alanine has a high negative correlation with all but the non-polar residues. We therefore propose the use of, for example, serine as a substitute for the residues that are negatively correlated with alanine.
Jonson
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PH
Biostructure and Protein Engineering Group, Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark.
Petersen
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D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D007477:Ions; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012997:Solvents / Q000494:pharmacology; D055672:Static Electricity
D007477:Ions; D012997:Solvents; D001224:Aspartic Acid; D018698:Glutamic Acid