Conformational analysis of macromolecules. V. Helical structures of poly-L-aspartic acid and poly-L-glutamic acid, and related compounds.

Abstract

Previous energy calculations for isolated (single-stranded) homopolymer polyamino acids, to find the most stable regular (helical) conformations, have been extended to poly-L-aspartic acid, poly-L-glutamic acid, and several related compounds. Since rotation about all single bonds (including the acid and ester groups of side chains) was taken into account, it was necessary to obtain expressions for the torsional potentials for these internal rotations. The computed helix sense was found to agree with the experimental one in all cases except one, using a single set of potential functions and parameters. The various contributions to the total energy are all important in their influence on the conformation. For most of the polymers studied, there are only four principal side-chain conformations of low energy, two for the right-handed and two for the left-handed helix sense. Essentially the same set of four conformations was found for poly-L-aspartic acid and all of its esters; a different set of four conformations was found for poly-L-glutamic acid and its esters. For any given polymer, the conformation of lowest energy (of the four general conformations) depended upon the details of the specific side chain involved. The side chain conformations can be classified as being either transverse, for which the side chains wrap tangentially about the backbone at right angles to the helix axis, or longitudinal, for which the side chains lie more nearly parallel to the helix axis. For most polymers, one transverse and one longitudinal conformation of low energy was found for each helix sense. For aspartate polymers with short side chains, the longitudinal conformations had lower energy than the transverse ones, but the converse was true for aspartate polymers with longer side chains (viz., the n-propyl and benzyl esters). This effect was primarily the result of competition between the torsional and nonbonded energies; the unfavorable torsional energy in the transverse conformation was compensated by a favorable nonbonded energy, provided that the side chain was long enough to lead to a large nonbonded side chain-to-backbone interaction. For the glutamate polymers, a longitudinal conformation (different from that of the aspartate polymers) was preferred in all cases for the right-handed helix sense, but a transverse one was of lower energy for the left-handed helix sense. Poly-l-phenylalanine was found to have essentially the same conformations as the previously reported conformations for poly-l-tyrosine; the χ1 and κ2 values for these conformations are close to those found for poly-l-aspartic acid. This conformational similarity can be accounted for in terms of the geometrical similarity between the side chains of phenylalanine, tyrosine, and aspartic acid.