In the course of rapid system prototyping of a large scale design and implementation of the BLAST algorithm for bioinformatics, we evaluated two dzfferent design methods. First, we used the "traditional" method of design with modeling in C and design and synthesis using VHDL. Second, we used the automated tools MATLAB/Simulink with two different designjlows, i.e. the fully automated one @om ILL4 TLAB to bitstream, and, the architecture and subsystem development based on the MATLAB/Simulink results. We examine the tradeoffs between designer time, design quality and speed, and resource optimization. We analyze how modern tools such as MTLAB/Simulink can improve architecture design and facilitate "what 17' scenarios. We conclude that conventional architecture development and design flow is still required for highly optimized system building but the architecture development capabilities of modern tools need to be assimilated in the design process.