Exploring protein sequence space using knowledge-based potentials.
Knowledge-based potentials can be used to decide whether an amino acid sequence is likely to fold into a prescribed native protein structure. We use this idea to survey the sequence-structure relations in protein space. In particular, we test the following two propositions which were found to be important for efficient evolution: the sequences folding into a particular native fold form extensive neutral networks that percolate through sequence space. The neutral networks of any two native folds approach each other to within a few point mutations. Computer simulations using two very different potential functions, M. Sippl's PROSA pair potential and a neural network based potential, are used to verify these claims.
Babajide
A
A
Institut für Theoretische Chemie und Molekulare Strukturbiologie, Universität Wien, Währingerstrasse 17, A-1090 Vienna, Austria.
Farber
R
R
Hofacker
I L
IL
Inman
J
J
Lapedes
A S
AS
Stadler
P F
PF
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D019143:Evolution, Molecular; D008956:Models, Chemical; D011487:Protein Conformation; D017510:Protein Folding