Title: A Double-Well Ultra-Coarse-Grained Model to Describe Protein Conformational Transitions

Authors: Yuwei Zhang, Zexing Cao, John Zeng Hui Zhang, and Fei Xia

Abstract: The double-well model is usually used to describe the conformational transition between two states of protein. Since conformational changes usually occur within a relatively large timescale, coarse-grained models are often used to accelerate the dynamic process due to its inexpensive computational cost. In this work, we develop a double-well ultra-coarse-grained (DW-UCG) model to describe the conformational transitions of the adenylate kinase, glutamine-binding protein and lactoferrin. The coarse-grained simulation results show that the DW-UCG model of adenylate kinase captures the crucial intermediate states in the LID-closing and NMP-closing pathways, reflecting the key secondary structural changes in conformational transition. A comparison of the different DW-UCG models of adenylate kinase indicates that an appropriate choice of bead resolution could generate the free energy landscape that is comparable to that from the residue-based model. The coarse-grained simulations for the glutamine-binding protein and lactoferrin also demonstrate that the DW-UCG model is valid in reproducing the correct two-state behaviour for their functional study, which indicate the potential application of the DW-UCG model in investigating the mechanism of conformational changes of large proteins.

Full-Link: https://pubs.acs.org/doi/10.1021/acs.jctc.0c00551