Polypeptide dynamics: Experimental tests of an optimized Rouse–Zimm type model

Abstract

A theory for long time random coil peptide dynamics is developed based on a generalization of the optimized Rouse–Zimm model of Perico et al. [J. Chem. Phys. 87, 3677 (1987)] and Perico [J. Chem. Phys. 88, 3996 (1988) and Biopolymers 28, 1527 (1989)]. The generalized model employs the rotational potential energy for specific amino acid residues and amino acid friction coefficients to compute all input parameters in the model. Calculations of the fluorescence depolarization correlation function P2(t ) and of the local persistence length are found to be sensitive to the amino acid sequence, the length of the polypeptide chain, and the location of the probe. Model computations of P2(t ) are compared with new experimentally determined rotational correlation times (of the order of nanoseconds) from fluorescence depolarization measurements of three different synthetic 17-residue peptides, each containing a single tryptophan (TRP) residue as a probe. In addition, the previous anisotropy measurements on ACTH, glucagon, and their fragments are discussed and compared with the model calculations. Our results indicate that the theory gives a reasonable prediction for the fluorescence depolarization correlation times of random coil polypeptides, but the calculated rotational correlation function predicts a much faster initial decay and a slower final decay than is observed. Possible theoretical improvements are discussed.