Computational investigation of the effect of thermal perturbation on the mechanical unfolding of titin I27

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• 作者：Navneet Bung (1)
  U. Deva Priyakumar (1) deva@iiit.ac.in
• 关键词：Protein folding – ; Steered molecular dynamics – ; Denaturation – ; Mechanical stability – ; Titin I27 – ; Folding pathways
• 刊名：Journal of Molecular Modeling
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：18
• 期：6
• 页码：2823-2829
• 全文大小：452.0 KB
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• 作者单位：1. Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, 500 032 India
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023

文摘

The emergence of single-molecule force measurement experiments has facilitated a better understanding of protein folding pathways and the thermodynamics involved. Computational methods such as steered molecular dynamics (SMD) simulations are helpful in providing atomistic level information on the unfolding pathways. Recent experimental studies have showed that combinations of single-molecule experiments with traditional methods such as chemical and/or thermal denaturation yield additional insights into the folding phenomenon. In this study, we report results from extensive computations (a total of about 60 SMD simulations with a total length of about 0.4 μs) that address the effect of thermal perturbation on the mechanical stability of the I27 domain of the protein titin. A wide range of temperatures (280–340 K) were considered for the pulling, which was done at both constant velocity and constant force using SMD simulations. Good agreement with experimental data, such as for the trends in changes in average force and the maximum force with respect to the temperature, was obtained. This study identifies two competing pathways for the mechanical unfolding of I27, and illustrates the significance of combining various techniques to examine protein folding.