Exploring protein sequence space using knowledge-based potentials

Knowledge-based potentials can be used to decide whether an amino. acid seq uence is likely to fold into a prescribed native protein structure. We use this idea to survey the sequence-structure relations in protein space. In p articular, we test the following two propositions which were found to be im portant for efficient evolution: the sequences folding into a particular na tive fold form extensive neutral networks that percolate through sequence s pace. The neutral networks of any two native folds approach each other to w ithin a few point mutations. Computer simulations using two very different potential functions, M. Sippl's PP,OSA pair potential and a neural network based potential, are used to verify these claims. (C) 2001 Academic Press.