Backmapping from Multiresolution Coarse-Grained Models to Atomic Structures of Large Biomolecules by Restrained Molecular Dynamics Simulations Using Bayesian Inference

Coarse-grained (CG) simulations have allowed access to larger length scales and longer time scales in the study of the dynamic processes of large biomolecules than all-atom (AA) molecular dynamics (MD) simulations. Backmapping from CG models to AA structures has long been studied because it enables us to gain detailed structure insights from CG simulations. Many methods first construct an AA structure from the CG model by fragments, random placement, or geometrical rules and subsequently optimize the solution via energy minimization, simulated annealing or position-restrained simulations. However, such methods may only work well on residue-level CG models and cannot consider the deviations of CG models. In this work, we describe, to the best of our knowledge, a new backmapping method based on Bayesian inference and restrained MD simulations. Restraints with log harmonic energy terms are defined according to the target CG model using the Bayesian inference in which the CG deviations can be estimated. From an initial AA structure obtained from either high-resolution experiments or homology modeling, a MD simulation with the aforementioned restraints is performed to obtain a final AA structure that is a backmapping of the target CG model. The method was validated using multiresolution CG models of the soluble extracellular region of the human epidermal growth factor receptor and was further applied to construct AA structures from CG simulations of the nucleosome core particle. The results demonstrate that our method can generate accurate AA structures of different types of biomolecules from multiple CG models with either residue-level resolution or much lower resolution than one-site-per-residue.