GRADIENT DISCONTINUITIES IN CALCULATIONS INVOLVING MOLECULAR-SURFACE AREA

The free energy of solvation of a polypeptide or a protein can be expr essed in terms of the accessible surface area of the molecule. Algorit hms for energy minimization or for molecular dynamics, which involve t he first derivatives of the energy, including the free energy of solva tion, are commonly used in the conformational analysis of proteins. Di scontinuities of the first derivatives, which occur in the accessible surface area and, hence, in the solvation energy, can cause serious nu merical problems. In this paper, we describe all the situations in whi ch the gradient of the molecular surface area becomes discontinuous.