MODELING AMINO-ACID SIDE-CHAINS .2. DETERMINATION OF POINT CHARGES FROM ELECTROSTATIC PROPERTIES - TOWARD TRANSFERABLE POINT-CHARGE MODELS

An analysis of the charge transferability from one naturally occurring amino acid side chain to another structurally similar one is presente d. Point charges fitted to the self-consistent-field ab initio electro static potential and to the potential created by distributed multipole series are compared, using split-valence type 6-31G* wave functions. SCF electrostatic potential-derived net atomic charges are transferab le only for polar fragments, where the contribution of the high-order terms of the multipole expansion is hidden by large low-order moments. For nonpolar fragments, where the high-order terms of the multipole e xpansion dominate, a limited number of off-atom charges must be includ ed in order to reproduce the higher-order moments and, hence, attain a reasonable transferability of the charge models. Conversely, a recent ly proposed method, consisting of an analytical fit of the multipolar part of the exact molecular electrostatic potential, allows calculatio ns to continue to be made within the framework of atom-centered point charges. This analytical procedure, nevertheless, provides a consisten t transferability from one molecule to another structurally related on e, together with poorer, but still acceptable, reproduction of the ele ctrostatic potential.