ESTIMATION OF ABSOLUTE AND RELATIVE ENTROPIES OF MACROMOLECULES USING THE COVARIANCE-MATRIX

A new method is reported for estimating absolute and relative entropies of conformers of a macromolecule. It is based on the evaluation of the covariance matrix of Cartesian positional coordinates obtainable by computer simulation and requires only calculation of a determinant. The approximation for the absolute entropy is derived using a quantum-mechanical approach and represents an upper limit for the quantum-mechanical entropy. Together with the easily accessible energy it offers a new way to calculate absolute and relative free energies of conformers. The numerical application of the method, which is of particular interest in the field of protein research, is demonstrated with the example of a short alpha-helical polypeptide.