TY - JOUR
T1 - Double-Well Ultra-Coarse-Grained Model to Describe Protein Conformational Transitions
AU - Zhang, Yuwei
AU - Cao, Zexing
AU - Zhang, John Zenghui
AU - Xia, Fei
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grants No. 21773065 21673185, and 21873078). We acknowledge the support of the NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the ECNU Public Platform for Innovation (001) for providing computer time.
Funding Information:
This work was supported by the National Natural Science Foundation of China (Grants No. 21773065, 21673185, and 21873078). We acknowledge the support of the NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the ECNU Public Platform for Innovation (001) for providing computer time.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/13
Y1 - 2020/10/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85092944645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092944645&partnerID=8YFLogxK
U2 - 10.1021/acs.jctc.0c00551
DO - 10.1021/acs.jctc.0c00551
M3 - Article
C2 - 32926616
AN - SCOPUS:85092944645
SN - 1549-9618
VL - 16
SP - 6678
EP - 6689
JO - Journal of chemical theory and computation
JF - Journal of chemical theory and computation
IS - 10
ER -