Single-particle 3D reconstruction from cryo-electron microscopy (cryo-EM) images is a kernel application of biological molecules analysis, as the computational requirement of which is now beyond PetaFlop for a high-resolution 3D structure. In this paper, we quantitatively analyze the workload, computational intensity and memory performance of the application, parallelize it on an emerging multicore architecture GPU-CUDA. Further we apply a percolation technique to decouple computation with memory operations and orchestrate thread-data mapping to reduce the overhead offchip memory operations. Finally we tested our optimization strategy on a popular open-source package EMAN to GPU-CUDA, which achieves a relative speedup of about 10X to the original CPU-only EMAN. The experimental results also show that the proposed percolation programming greatly improves utilization of memory bandwidth and floating-point units. Categories and Subject Descriptors C.4 [Computer Systems Organization ]: ...