Functional full-system simulators are powerful and versatile research tools for accelerating architectural exploration and advanced software development. Their main shortcoming is limited throughput when simulating systems with hundreds of processors or more. To overcome this bottleneck, we propose the PROTOFLEX simulation architecture, which uses FPGAs to accelerate simulation. Prior FPGA approaches that prototype a complete system in hardware are either too complex when scaling to large-scale configurations or require significant effort to provide full-system support. In contrast, PROTOFLEX reduces complexity by virtualizing the execution of many logical processors onto a consolidated set of multiple-context execution engines on the FPGA. Through virtualization, the number of engines can be judiciously scaled, as needed, to deliver on necessary simulation performance. To achieve low-complexity full-system support, a hybrid simulation technique called transplanting allows implementing in the FPGA only the frequently encountered behaviors, while a software simulator preserves the abstraction of a complete system We have created a first instance of the PROTOFLEX simulation architecture, which is an FPGA-based, full-system functional simulator for a 16-way UltraSPARC III symmetric multiprocessor server hosted on a single Xilinx Virtex-II XCV2P70 FPGA. On average, the simulator achieves a 39x speedup (and as high as 49x) over comparable software simulation across a suite of applications, including OLTP on a commercial database server.