Folding Lennard-Jones proteins by a contact potential

We studied the possibility to approximate a Lennard-Jones interaction by a pairwise contact potential. First we used a Lennard-Jones potential to desi gn off-lattice, protein-like heteropolymer sequences, whose lowest energy ( native) conformations were then identified by molecular dynamics. Then we t urned to investigate whether one can find a pairwise contact potential, who se ground states are the contact maps associated with these native conforma tions. We show that such a requirement cannot be satisfied exactly, i.e., n o such contact parameters exist. Nevertheless, we found that one can find c ontact energy parameters for which an energy minimization procedure, acting in the space of contact maps, yields maps whose corresponding structures a re close to the native ones. Finally, we show that when these structures ar e used as the initial point of a molecular dynamics energy minimization pro cess, the correct native folds are recovered with high probability. Protein s 1999;37:544-553. (C) 1999 Wiley-Liss, Inc.