The effect of chain conformation change on the self-assembly behavior of poly(gamma-benzyl-L-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) was studied both experimentally by transmission electron microscopy, laser light scattering, and circular dichroism and computationally using molecular dynamics (MD) simulation. It was found that, by introducing trifluoroacetic acid to the PBLG-b-PEG solution, the conformation of the PBLG chain transforms from a-helix to random coil, which results in a change of the micelle structures formed by PBLG-b-PEG from rod to sphere. Meanwhile, the MD simulations were performed by using Brownian dynamics on the self-assembly behavior of model AB-type diblock copolymers with various chain rigidities of the A-block. The results show that, by decreasing the fraction of rigid chain conformation of the A-block, which corresponds to the helix-coil transition in the PBLG-b-PEG sample, the aggregate structure transforms from rod to sphere. The MD simulations also provide chain packing information in the micelles. On the basis of both experimental and MD simulation results, the mechanism regarding the effect of the conformation change of the polypeptide block copolymer on its self-association behavior is suggested.