SimAtomic Blog

KRAS G12D Cryptic Pocket Discovery: Multi-Microsecond MD with Enhanced Sampling

KRAS mutations drive approximately 25% of all human cancers, with the G12D mutation being one of the most prevalent oncogenic variants. Despite decades of research, KRAS has remained largely "undruggable" due to its smooth surface and lack of traditional binding pockets. However, recent advances in molecular dynamics (MD) simulations suggest that cryptic pockets—transient binding sites that emerge during protein dynamics—may offer new therapeutic opportunities.

In this case study, we present our approach to discovering cryptic binding pockets in the active KRAS G12D mutant using multi-microsecond molecular dynamics simulations enhanced with advanced sampling techniques.

Benchmarking GPUs for MD Simulations: Speed and Cost Insights from SimAtomic

Molecular dynamics (MD) simulations are notoriously computationally intensive, especially when run with explicit solvent. GPUs have become essential for accelerating MD engines like OpenMM, offering order-of-magnitude speedups over CPUs [1].

SimAtomic collaborated with Shadeform, a marketplace providing access to GPU instances across 20+ cloud providers, to benchmark a range of GPU instance types. Here are the results...

Wetlab Savings with Molecular Dynamics Rescoring

Adding a short molecular-dynamics (MD) step after docking in virtual drug screening can cut wet-lab costs by > 50 %. Savings that matter especially for startups and small biotechs needing to stretch their runway, yet few are using it.

Democratizing Access to Advanced Computational Tools

Advanced computational tools for drug discovery have traditionally been accessible only to large pharmaceutical companies with significant resources. This has created a barrier for smaller biotech companies and academic researchers who could benefit from these technologies.

Here we present how our open-source package streamlines MD simulation setup and execution.