Several approaches have been proposed to alleviate these shortcoming of the MFCC method and to improve its accuracy. Some additional interactions can be accounted for by using larger fragments consisting of more than one amino acid or by using additional caps to model the severed hydrogen bonds . In a similar spirit, numerous energy-based fragmentation methods using overlapping fragments have been pro-posed , which approach the accuracy of the full supermolecular calculation as the size of the fragments is enlarged. Alternatively, interactions between fragments can be partly included in the MFCC method by using a classical electrostatic or density-based embedding scheme.