Exploring Protein Sequence Space Using Knowledge Based Potentials


Aderonke Babajide, Robert Farber, Ivo L. Hofacker, Jeff Inman, Alan S. Lapedes, and Peter F. Stadler

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.

Submitted to Prot.Sci..

Keywords: Knowledge-Based Potentials, Inverse Folding, Neutral Networks, Protein Evolution

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