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An implementation of hydrophobic force in implicit solvent molecular dynamics simulation for packed proteins

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Abstract

MD simulations of five proteins in which helical chains are held together by hydrophobic packing were carried out to investigate the effect of hydrophobic force on simulated structures of these protein complexes in implicit generalized Born (GB) model. The simulation study employed three different methods to treat hydrophobic effect: the standard GB method that does not include explicit hydrophobic force, the LCPO method that includes explicit hydrophobic force based directly on solvent accessible surface area (SASA), and a proposed packing enforced GB (PEGB) method that includes explicit hydrophobic force based on the radius of gyration of the protein complex. Our simulation study showed that all five protein complexes were unpacked in the standard GB simulation (without explicit hydrophobic force). In the LCPO method, three of the five protein systems remained well packed during the simulation, indicating the need for an explicit hydrophobic force in GB model for these packed protein systems. However, two of the five systems were still unpacked during LCPO simulation. For comparison, all five protein systems remain well packed in simulation using the new PEGB method. Analysis shows that the failure of the LCPO method in two cases is related to the way that SASA changes during the unpacking process for these two systems. These examples showed that standard GB method without explicit hydrophobic force is not suitable for MD simulation of protein systems involving hydrophobic packing. A similar problem remains but to a much lesser extent in the LCPO method for some packed protein systems. The proposed PEGB method seems quite promising for MD simulation of large, multi-domain packed proteins in implicit solvent model.

The native structure of a hydrophobically packed protein is better preserved under packing enforced generalized Born model than other models

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Acknowledgments

L.L.D. is grateful to the National Natural Science Foundation of China (Grants 11147026 and 31200545) and the Scientific Research Award Fund for the Excellent Middle-Aged and Young Scientists of Shandong Province (Grant BS2011SW046) for support. Y.M. was supported by the Shanghai Rising-Star program (Grant11QA1402000). Q.G.Z. thanks the National Natural Science Foundation of China (Grant 11274206) for support. B.T. was supported by 973 Program (2013CB933800) and the National Key Natural Science Foundation of China (Grants 21035003 and 21227005). J.Z.H.Z. acknowledges financial support from the National Natural Science Foundation of China (Grants 10974054 and 20933002) and the Shanghai PuJiang program (Grant 09PJ1404000). We thank the Supercomputer Center of East China Normal University for CPU time support.

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Authors and Affiliations

  1. College of Physics and Electronics, Shandong Normal University, Jinan, 250014, China

    Li L. Duan & Qing G. Zhang

  2. State Key Laboratory of Precision Spectroscopy and Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, 200062, China

    Tong Zhu, Ye Mei & John Z. H. Zhang

  3. College of Chemistry, Chemical Engineering and Materials Science, Engineering Research Center of Pesticide and Medicine Intermediate Clean Production, Ministry of Education, Key Laboratory of Molecular and Nano Probes, Shandong Normal University, Jinan, 250014, China

    Li L. Duan & Bo Tang

  4. Department of Chemistry, New York University, New York, NY, 10003, USA

    John Z. H. Zhang

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  1. Li L. Duan
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  2. Tong Zhu
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Correspondence to Ye Mei or John Z. H. Zhang.

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Duan, L.L., Zhu, T., Mei, Y. et al. An implementation of hydrophobic force in implicit solvent molecular dynamics simulation for packed proteins. J Mol Model 19, 2605–2612 (2013). https://doi.org/10.1007/s00894-013-1798-8

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  • DOI: https://doi.org/10.1007/s00894-013-1798-8

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