G. Trinquier et Yh. Sanejouand, WHICH EFFECTIVE PROPERTY OF AMINO-ACIDS IS BEST PRESERVED BY THE GENETIC-CODE, Protein engineering, 11(3), 1998, pp. 153-169
Simple procedures are proposed to quantify how much an effective prope
rty embodied in a given ranking of the twenty amino acids can be affec
ted by random point mutations at nucleotide bases. As expected, of the
various orderings tested, rankings based on most hydrophobicity scale
s exhibit low scores, thus offering better immunity towards such singl
e-base mutations. This, however, occurs to different extents and the m
ethod allows sharp discriminations between the scales. Hydrophobicity
scales based on global properties such as spatial environment data of
proteins residues, or mutation matrices of amino acid replacements, ge
nerally behave better than those based on pure physicochemical propert
ies of isolated residues. An averaged scale built from the available h
ydrophobicity scales exhibits one of the most favorable scores. A syst
ematic search for the best amino acid order has been carried out acros
s all possible scales. Optimized scales are characterized by the exist
ence of a clustering scheme into three zones, within which permutation
s are more or less tolerated, depending on the zone and on the summati
on procedure used in the score calculation, The first cluster correspo
nds to the hydrophobic side, and includes the ten amino acids WMCFILVG
RS, Next follows the ATP triad. The third cluster coincides with the h
ydrophilic side and includes, in the last seven positions, the amino a
cids EDKNQHY. Interpretation of these optimized scales in terms of cod
on positions in the genetic code further suggests a clustering scheme
composed of four groups, WMCFILV-GRS-ATP-EDKNQHY, emphasizing the role
of the second base as the main driving parameter. As a consequence, t
he conserved character of the genetic code is better reflected when it
is displayed in UGCA ordering rather than in the commonly used UCAG o
rdering. The present a priori classification of the amino acids could
find potential use in protein sequence homology and structure predicti
on.