Computational modeling of protein conformational changes - Application to the opening SARS-CoV-2 spike

Highlights: • Introduce a new hybrid framework for the simulation of proteins' electro-geometric properties. • Combine Markov states models simulation with continuum modeling to obtain dynamical electric potential maps. • Construct new a posteriori error estimates for biomolecular computations. • Reveal and characterize variations of the electro-geometric properties of the SARS-CoV-2 spike protein as it opens. We present a new approach to compute and analyze the dynamical electro-geometric properties of proteins undergoing conformational changes. The molecular trajectory is obtained from Markov state models, and the electrostatic potential is calculated using the continuum Poisson-Boltzmann equation. The numerical electric potential is constructed using a parallel sharp numerical solver implemented on adaptive Octree grids. We introduce novel a posteriori error estimates to quantify the solution's accuracy on the molecular surface. To illustrate the approach, we consider the opening of the SARS-CoV-2 spike protein using the recent molecular trajectory simulated through the Folding@home initiative. We analyze our results, focusing on the characteristics of the receptor-binding domain and its vicinity. This work lays the foundation for a new class of hybrid computational approaches, producing high-fidelity dynamical computational measurements serving as a basis for protein bio-mechanism investigations.