GoToCloud: Development and future of the cloud-based platform for cryo-EM structure-based drug DesignDevelopment and...

The "Resolution Revolution" in cryogenic electron microscopy (Cryo-EM) has fundamentally advanced structure-based drug design (SBDD), moving beyond static snapshots to dynamic conformational analysis. However, the resulting exponential growth in data volume has created critical computational bottlenecks where traditional on-premise high-performance computing lacks necessary scalability and economic flexibility. This chapter describes "GoToCloud," a platform leveraging Amazon Web Services (AWS) ParallelCluster to overcome these barriers. We introduce a "Shared EFS" architecture and automated scripts allowing researchers to deploy secure virtual clusters within a Virtual Private Cloud (VPC), pre-installed with essential software like RELION. This design eliminates specialized IT maintenance needs for researchers using Cryo-EM while ensuring consistent analysis environments across distributed groups. Extensive benchmarking using practical datasets, including Nitrite Reductase and Streptavidin, validates the platform's effectiveness. Crucially, we provide a detailed economic analysis optimizing cost-performance by identifying specific GPU instance types (e.g., NVIDIA T4 vs. A10G) that balance processing speed with expense. The platform achieved 1.83Å resolution, revealing the "2.0Å wall" for cost-performance. Additionally, the platform addresses global data logistics by integrating Zettar zx, a high-speed transfer technology utilizing burst-buffer architecture. This successfully demonstrated ∼4.6 Gbps throughput over intercontinental distances despite 10 Gbps on-premise bottlenecks, replacing slow physical media transport. By democratizing access to High-Performance Computing (HPC) and enabling rapid data mobility, GoToCloud establishes a robust foundation for next-generation SBDD, facilitating fully automated high-throughput screening and experimental validation of AI-predicted models.