Modeling hydrogen exchange of proteins by a multiscale method* *Project supported by the National Natural Science Foundation of China (Grant Nos. 11974173 and 11934008) and the HPC Center of Nanjing University.

Abstract

We proposed a practical way for mapping the results of coarse-grained molecular simulations to the observables in hydrogen change experiments. By combining an atomic-interaction based coarse-grained model with an all-atom structure reconstruction algorithm, we reproduced the experimental hydrogen exchange data with reasonable accuracy using molecular dynamics simulations. We also showed that the coarse-grained model can be further improved by imposing experimental restraints from hydrogen exchange data via an iterative optimization strategy. These results suggest that it is feasible to develop an integrative molecular simulation scheme by incorporating the hydrogen exchange data into the coarse-grained molecular dynamics simulations and therefore help to overcome the accuracy bottleneck of coarse-grained models.