Protein structure alignment is one of the fundamental problems in computational structure biology. A variety of algorithms have been developed to address this important issue in the past decade. However, due to their heuristic nature, current structure alignment methods all more or less suffer from suboptimal alignment and/or over-fragmentation and may lead to a biologically wrong alignment. To overcome these limitations, we have developed an accurate topology-independent and global structure alignment method through an FFT-based exhaustive search algorithm, which is referred to as FTAlign.