The response of the internal dynamics of a polypeptide to changes in its amino acid (aa) composition was investigated by applying the florescence blob model (FBM) to a series of pyrene-labeled poly(D,L-alanine-co-D,L-glutamic acid)s (PAlaGAs) and poly(D,L-glutamic acid) (PGA). The alanine content of the PAlaGA samples was varied between 24 and 58 mol % by using PGA (containing 0 mol % alanine) for comparison purposes. The FBM yielded the number N-blob of aa's that could diffusively encounter one another in a blob, which is the volume probed by an excited pyrenyl label covalently attached to the polypeptide. The incorporation of 24 mol % of alanine was found to significantly increase N-blob from 11 +/- 1 for PGA to 16 +/- 1 for the Pala(24)GA(76) sample in DMSO due to the enhanced conformational freedom provided by alanine to the polypeptide. Interestingly, further increases in the alanine content of the PAlaGA samples from 24 to 58 mol % did not change the N-blob value, implying that only a few flexible aa's in the backbone of a polypeptide are required to disrupt its rigid conformation. The N-blob values of 16 for PAlaGA and 23 found earlier for poly(glycine-co-D,L-glutamic acid) (PGlyGA) were then used to estimate an average N-blob value of 19 aa's for proteins based on their average aa composition, which should include at least one glycine or one alanine residue for a blob of this size. The N-blob value of 19 aa's was then used to estimate the folding times of 145 different proteins by applying a simple hierarchical conformational search method to determine the number of conformations that could be adopted by the oligopeptide segment of a protein located inside a blob. Surprisingly for such a crude and simple approach, the method provided folding time (tau(F)) estimates that were in good agreement with experimentally measured values, resulting in a correlation coefficient of 0.73. The good agreement found between the calculated and experimentally determined tau(F)'s supports the notion that the folding of proteins occurs in and among localized subdomains which happen to be well represented by a FBM analysis of the fluorescence decays of pyrene-labeled polypeptides.