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...

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Veröffentlicht in:Protein engineering 2001-06, Vol.14 (6), p.397-402
Hauptverfasser: Jonson, Per Harald, Petersen, Steffen B.
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container_title Protein engineering
container_volume 14
creator Jonson, Per Harald
Petersen, Steffen B.
description 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.
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current)
subjects amino acid properties
Amino Acid Sequence
Aspartic Acid - chemistry
Glutamic Acid - chemistry
Ions
Models, Molecular
Mutation
Protein Conformation
protein engineering
Sequence Homology, Amino Acid
solvent accessibility
Solvents - pharmacology
spatial contacts
Static Electricity
structural preference
title A critical view on conservative mutations
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