Amino acid similarity matrices based on force fields.
BACKGROUND
We propose a general method for deriving amino acid substitution matrices from low resolution force fields. Unlike current popular methods, the approach does not rely on evolutionary arguments or alignment of sequences or structures. Instead, residues are computationally mutated and their contribution to the total energy/score is collected. The average of these values over each position within a set of proteins results in a substitution matrix.


RESULTS
Example substitution matrices have been calculated from force fields based on different philosophies and their performance compared with conventional substitution matrices. Although this can produce useful substitution matrices, the methodology highlights the virtues, deficiencies and biases of the source force fields. It also allows a rather direct comparison of sequence alignment methods with the score functions underlying protein sequence to structure threading.


BACKGROUND
Example substitution matrices are available from http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html.


BACKGROUND
The list of proteins used for data collection and the optimized parameters for the alignment are given as supplementary material at http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html.
Dosztányi
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Z
Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia. zsuzsa@rsc.anu.edu.au
Torda
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D019943:Amino Acid Substitution; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019295:Computational Biology; D009154:Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment / Q000706:statistics & numerical data; D013816:Thermodynamics
D011506:Proteins