Proteins with selected sequences fold into unique native conformation

We design sequences of 80-monomer model protein which provide very low energy in the target (‘‘native’’) structure. Then the designed sequence is subjected to lattice Monte Carlo simulation of folding. In all runs model protein folded from random coil to the unique native conformation, effectively ‘‘solving’’ the multiple minima problem. These results suggest that thermodynamically oriented selection of sequences which makes the native conformation a pronounced deep minimum of energy solves the problem of kinetic accessibility of this conformation as well.