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Molecular dynamics simulations on HIV-1 Tat

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Abstract

Molecular dynamics simulations are used to investigate dynamics and intramolecular interactions of the HIV-1 transactivator (Tat) in aqueous solution. The calculations are based on the AMBER force field with particle mesh Ewald treatment for long-range electrostatics. The Tat structure exhibits a large flexibility, consistent with its absence of secondary structure elements. From an analysis of the correlation matrix and of electrostatic interactions we suggest that segments expressed by the two exons (amino acids 1–72 and 73–86, respectively) exhibit rather separated dynamic and energetic properties. We also identify intramolecular interactions of importance for structure stabilization. In particular, significant electrostatic interactions are recognized between the N-terminus and the basic domain of the protein, consistent with site-directed mutagenesis performed in this work.

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Notes

  1. Since Glu has the same charge as Asp and it has a longer side chain, its interactions with the ARD residues are expected to be at least as strong as those formed by Asp2 in the HV1Z2 variant.

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Acknowledgements

COFIN-MURST is acknowledged for financial support. We thank U. Rothlisberger and L. Guidoni for useful discussions.

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Authors and Affiliations

  1. International School for Advanced Studies (ISAS) and INFM, DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Via Beirut 2–4, 34014 , Trieste, Italy

    Sergio Pantano & Paolo Carloni

  2. Molecular Medicine Laboratory, International Center for Genetic Engineering and Biotechnology, Padriciano 99, 34012 , Trieste, Italy

    Mudit Tyagi & Mauro Giacca

  3. Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100 , Pisa, Italy

    Mudit Tyagi & Mauro Giacca

  4. IMASL, CONICET, National University of San Luis, Ejercito de los Andes 950, CP 5700, San Luis, Argentina

    Sergio Pantano

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  1. Sergio Pantano
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  2. Mudit Tyagi
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  3. Mauro Giacca
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  4. Paolo Carloni
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Correspondence to Paolo Carloni.

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Pantano, S., Tyagi, M., Giacca, M. et al. Molecular dynamics simulations on HIV-1 Tat. Eur Biophys J 33, 344–351 (2004). https://doi.org/10.1007/s00249-003-0358-z

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