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

YW Zhang and Z Cao and JZ Zhang and F Xia, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 16, 6678-6689 (2020).

DOI: 10.1021/acs.jctc.0c00551

The double-well model is usually used to describe the conformational transition between two states of a protein. Since conformational changes usually occur within a relatively large time scale, coarse-grained models are often used to accelerate the dynamic process due to their 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 the 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 behavior for their functional study, which indicates the potential application of the DW-UCG model in investigating the mechanism of conformational changes of large proteins.

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