m>ff14IDPsm> force field improving the conformation sampling of intrinsically disordered proteins

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• 作者：Dong Song ; Wei Wang ; Wei Ye ; Dingjue Ji ; Ray Luo and Hai-Feng Chen
• 刊名：Chemical Biology & Drug Design
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：89
• 期：1
• 页码：5-15
• 全文大小：1771K
• ISSN：1747-0285

文摘

Intrinsically disordered proteins are proteins which lack of specific tertiary structure and unable to fold spontaneously without the partner binding. These intrinsically disordered proteins are found to associate with various diseases, such as diabetes, cancer, and neurodegenerative diseases. However, current widely used force fields, such as m>ff99SBm>,m> ff14SBm>,m> OPLS/AAm>, and m>Charmm27m>, are insufficient in sampling the conformational characters of intrinsically disordered proteins. In this study, the CMAP method was used to correct the m>φm>/m>ψm> distributions of disorder-promoting amino acids. The simulation results show that the force filed parameters (m>ff14IDPsm>) can improve the m>φm>/m>ψm> distributions of the disorder-promoting amino acids, with RMSD less than 0.10% relative to the benchmark data of intrinsically disordered proteins. Further test suggests that the calculated secondary chemical shifts under m>ffm>14IDPs are in quantitative agreement with the data of NMR experiment for five tested systems. In addition, the simulation results show that m>ff14IDPsm> can still be used to model structural proteins, such as tested lysozyme and ubiquitin, with better performance in coil regions than the original general Amber force field m>ff14SBm>. These findings confirm that the newly developed Amber m>ffm>14IDPs is a robust model for improving the conformation sampling of intrinsically disordered proteins.