Amino acid exchangeability from experimental data
Arlin Stoltzfus
Center for Advanced Research in Biotechnology, NIST
Tuesday, April 9, 2002 15:00-16:00,
Room 145, NIST North (820)
Gaithersburg
Tuesday, April 9, 2002 13:00-14:00,
Room 4511
Boulder
Abstract:
Patterns of amino acid sequence change in proteins are often
interpreted by reference to a pairwise measure of amino acid distance,
based either on some biophysical model of effects, or more commonly on
propensities of evolutionary change. Though both types of measure are
useful, the first is based on an uncertain estimation of the role of amino
acid chemistry in a protein environment, and the second, though it
naturally reflects this role, confounds protein effects with unrelated
evolutionary factors, particularly genetic mutation between codons. To
separate the exchangeability of amino acids in proteins from effects of
the mutational interchangeability of codons, a measure of amino acid
exchangeability has been computed from results of 9695 experimental amino
acid exchanges from 12 experimental studies in which amino acids were
exchanged systematically. A frequency distribution of the quantitative
effects of amino acid exchanges on protein activity is derived from the
data and used as the basis for transforming results of different studies
to a common scale. Combining the results of all 12 studies yields a
nearly complete matrix of exchangeability, here called EX. The power of
this measure has been evaluated, in comparison to available measures of
amino acid distance, by a jack-knife procedure in which 11 studies are
used to predict the results of the 12th study. In limited tests done
so far, EX out-performs commonly used alternatives, including divergence-
based matrices (PAM, BLOSUM), an ad hoc matrix based on physicochemical
properties of amino acids (Grantham), and a physics-based model of mean
effect estimated from structural data (Miyazawa-Jernigan). In combination
with models of the mutation spectrum, EX may prove useful in teasing
apart the separate influences of mutation and selection on codon usage,
amino acid composition, and protein sequence evolution.
Contact: F. HuntNote: Visitors from outside NIST must contact
Robin Bickel; (301) 975-3668;
at least 24 hours in advance.
|
