ESTIMATION OF ABSOLUTE AND RELATIVE ENTROPIES OF MACROMOLECULES USINGTHE COVARIANCE-MATRIX

A new method is reported for estimating absolute and relative entropie s of conformers of a macromolecule. It is based on the evaluation of t he covariance matrix of Cartesian positional coordinates obtainable by computer simulation and requires only calculation of a determinant. T he approximation for the absolute entropy is derived using a quantum-m echanical approach and represents an upper limit for the quantum-mecha nical 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 inte rest in the field of protein research, is demonstrated with the exampl e of a short alpha-helical polypeptide.