Exploration of the Misfolding Mechanism of Transthyretin Monomer: Insights from Hybrid-Resolution Simulations and Markov State Model Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Initial Structures
2.2. Molecular Dynamics Simulations
2.3. Markov State Model and Construction and Validation
2.4. Dynamical Cross-Correlation Map Analysis
3. Results and Discussion
3.1. Comparison of PACE Simulation and All-Atom Simulation
3.2. Validation of Constructed Markov State Model
3.3. Structural Ensemble of Key States of Transthyretin Monomer Misfolding
3.4. Insights into the Misfolding Mechanisms of TTR Monomer
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Zhou, S.; Cheng, J.; Yang, T.; Ma, M.; Zhang, W.; Yuan, S.; Lo, G.V.; Dou, Y. Exploration of the Misfolding Mechanism of Transthyretin Monomer: Insights from Hybrid-Resolution Simulations and Markov State Model Analysis. Biomolecules 2019, 9, 889. https://doi.org/10.3390/biom9120889
Zhou S, Cheng J, Yang T, Ma M, Zhang W, Yuan S, Lo GV, Dou Y. Exploration of the Misfolding Mechanism of Transthyretin Monomer: Insights from Hybrid-Resolution Simulations and Markov State Model Analysis. Biomolecules. 2019; 9(12):889. https://doi.org/10.3390/biom9120889
Chicago/Turabian StyleZhou, Shuangyan, Jie Cheng, Ting Yang, Mingyue Ma, Wenying Zhang, Shuai Yuan, Glenn V. Lo, and Yusheng Dou. 2019. "Exploration of the Misfolding Mechanism of Transthyretin Monomer: Insights from Hybrid-Resolution Simulations and Markov State Model Analysis" Biomolecules 9, no. 12: 889. https://doi.org/10.3390/biom9120889