Protein folding with a reduced model and inaccurate short-range restraints

A reduced high-coordination lattice protein model and the Replica Exchange Monte Carlo sampling were employed in de novo folding simulations of a set of representative small proteins. Three distinct situations were analyzed. In the first series of simulations, the folding was controlled purely by the generic force field of the model. In the second, a bias was introduced towards the theoretically predicted secondary structure. Finally, we superimposed soft restraints towards the native-like local conformation of the backbone. The short-range restraints used in these simulations are based on approximate values of phi and psi dihedral angles, which may simulate restraints derived from inaccurate experimental measurements. Incorporating such data into the reduced model required developing a procedure, which transforms the phi and psi coordinates into coordinates of the protein alpha carbon trace. It has been shown that such limited data are sufficient for de novo determination of three-dimensional structures of small and topologically not too complex proteins.