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Molecular dynamics simulations of ribonuclease T1

Effect of solvent on the interaction with 2′GMP

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Abstract

Molecular dynamics simulations in vacuum and with a water sphere around the active site were performed on the 2′GMP-RNase T1 complex. The presence of water led to the maintenance of the 2′-GMP-RNase T1 interactions as compared to the X-ray structure, including the hydrogen bonds implicated in the enzyme-inhibitor recognition process. The sidechain of His92 in the molecular dynamics water simulation, however, hydrogen bonds directly to the phosphate of 2′GMP in contrast to the X-ray structure but in support of the role of that residue in the enzyme's catalytic mechanism. Fluctuations of activesite residues are not strongly influenced by water, possibly owing to the exclusion of water by the bound 2′GMP, which did show an increase in mobility. Analysis of the 2′GMP-RNase T1 interactions versus time reveal an equilibrium fluctuation in the presence of water, leading to a less favorable 2′GMP-RNase T1 interaction energy, suggesting a possible relationship between picosecond fluctuations and inhibitor dissociation occurring in the millisecond time domain.

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Abbreviations

RNase T1:

Ribonuclease T1 (EC.3.1.27.3)

2′GMP:

Guanosine-2′-monophosphate

SBS:

Stochastic Bondary Simulation

VS:

Vacuum Simulation

MD:

Molecular Dynamics

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Author notes

  1. A. D. MacKerell Jr.

    Present address: Department of Chemistry, Harvard University, 12 Oxford Street, 02138, Cambridge, Massachusetts, USA

Authors and Affiliations

  1. Department of Medical Biophysics, Karolinska Institutet, S-104 01, Stockholm, Sweden

    A. D. MacKerell Jr., R. Rigler & L. Nilsson

  2. Institute for Crystallography, Free University Berlin, Takustrasse 6, D-1000, Berlin, Germany

    U. Heinemann & W. Saenger

Authors
  1. A. D. MacKerell Jr.
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  2. R. Rigler
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  3. L. Nilsson
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  4. U. Heinemann
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  5. W. Saenger
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MacKerell, A.D., Rigler, R., Nilsson, L. et al. Molecular dynamics simulations of ribonuclease T1. Eur Biophys J 16, 287–297 (1988). https://doi.org/10.1007/BF00254065

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  • DOI: https://doi.org/10.1007/BF00254065

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