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Structural implications of mutations assessed by molecular dynamics: Vpu1–32 from HIV-1

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Abstract

Structural pore models are generated for Vpu1–32WT from HIV-1 as well as for three mutants W23L, S24L and R31V. A computational methodology is employed which samples the whole conformational space of the pentameric assemblies of Vpu. The analysis of the related energy landscape reveals a small set of reasonable pore models, which are thoroughly investigated regarding their structural properties as well as their putative stability under native-like conditions. The models are also discussed in respect of earlier experimental findings about their channel activities. The study proposes functional pores reflecting the experimentally found conductance states of Vpu and its mutants.

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Acknowledgment

WBF acknowledges National Yang-Ming University and the government of Taiwan for financial support (Aim of Excellence Program), as well as the National Science Council of Taiwan (NSC). J.K. acknowledges a fellowship granted jointly by the Alexander von Humboldt-Foundation and NSC. We thank the Paderborn Center for Parallel Computing PC2 (http://wwwcs.uni-paderborn.de/pc2/) for providing computer time.

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Authors and Affiliations

  1. Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei, 112, Taiwan

    J. Krüger & Wolfgang B. Fischer

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  1. J. Krüger
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  2. Wolfgang B. Fischer
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Correspondence to Wolfgang B. Fischer.

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Viral membrane proteins, Heidelberg, December 2008.

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Krüger, J., Fischer, W.B. Structural implications of mutations assessed by molecular dynamics: Vpu1–32 from HIV-1. Eur Biophys J 39, 1069–1077 (2010). https://doi.org/10.1007/s00249-009-0487-0

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  • DOI: https://doi.org/10.1007/s00249-009-0487-0

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