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Molecular dynamics simulation of the renin inhibitor H142 in water

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Summary

H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a-Leu-Val-peptide bond (i. e. C(=O)-NH→CH2-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding.

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Authors and Affiliations

  1. Department of Physical Chemistry 2, Chemical Centre, Lund University, P.O.B. 124, S-221 00, Lund, Sweden

    Olle Teleman

  2. Department of Physical Chemistry, Umeå University, S-901 87, Umeå, Sweden

    Maria Lindberg

  3. Department of Food Technology, Chemical Centre, Lund University, P.O.B. 124, S-221 00, Lund, Sweden

    Sven Engström

Authors
  1. Olle Teleman
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  2. Maria Lindberg
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  3. Sven Engström
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Teleman, O., Lindberg, M. & Engström, S. Molecular dynamics simulation of the renin inhibitor H142 in water. J Computer-Aided Mol Des 5, 187–203 (1991). https://doi.org/10.1007/BF00124338

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  • DOI: https://doi.org/10.1007/BF00124338

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