PROTEIN-FOLDING AND FOLD RECOGNITION FOR SQUARE LATTICE MODELS

Protein folding and inverse protein folding problems are examined for the extremely simplified model of short self-avoiding square lattice w alks involving only two or three residue types. Simple interresidue co ntact free energy functions are given and are used to determine which sequences fold uniquely to which conformations. Contrary to general th eories of protein folding, this model system shows little correlation between free energy and conformational distance from the native, nor i s there any marked energy gap between the native and the best non-nati ve structures. Furthermore, even the given free energy function someti mes fails to identify which sequences fold to a particular target stru cture. If current ideas about protein folding and structure/sequence c ompatibility fail in this model system, it is unclear why they should be valid for real proteins.