An innovative reconfiguration application is proposed to re-calculate the parameters of the Ferragina and Manzini exact search algorithm (or FM indexes), using a modular and efficient hardware implementation to accelerate alignment programs of short DNA sequence reads. Although these programs use multi-core execution strategies or multiple computers, they have become slow considering the very high speed at which the new massively parallel sequencing machines produce the reads to be aligned. Consequently, a search for different ways to accelerate the alignment is crucial. The proposed design runs with software functions in a hybrid system, and has the ability to align millions of reads to reference as large as the human genome. Tests on the M505k325t card show that a single alignment core can accelerate the computation by a factor close to [Formula: see text] in relation to BWA. Due to the minor consumption of area and power, multiple alignment cores can fill the Field Programmable Gate Array (FPGA) by multiplying the computation speed. With a multiple-core implementation, the processing speed of the design outperforms applications that are accelerated by GPUs and competes with similar FPGA proposals whose cost is much higher.