Using simplified protein representation as a reference potential for all-atom calculations of folding free energy

An effective approach for evaluating folding free-energy surfaces of explic it all-atom models is developed and examined. This approach is based on usi ng the potential of a simplified protein model as a reference potential for calculating the free energy of the corresponding explicit model. Prelimina ry results are presented for the folding free energy of a 12-residue helix. The potential of the method for studies of protein-folding processes is di scussed, emphasizing the ability to determine the difference between the re sults of simplified and explicit models. This can help in establishing the validity of simplified folding models.