Molecular dynamics simulations of the active matrix metalloproteinase-2: positioning of the N-terminal fragment and binding of a small peptide substrate

Proteins
Natalia Díaz, Dimas Suárez

Abstract

Herein we use different computational methods to study the structure and energetic stability of the catalytic domain of the active MMP-2 enzyme considering two different orientations of its N-terminal coil. The first orientation is largely solvent accessible and corresponds to that observed in the 1CK7 crystal structure of the proenzyme. In the second orientation, the N-terminal coil is packed against the Omega-loop and the alpha3-helix of the MMP-2 enzyme likewise in the so-called "superactivated" form of other MMPs. Binding to the MMP-2 catalytic domain of a short peptide substrate, which mimics the sequence of the alpha1 chain of collagen type I, is also examined considering again the two configurations of the N-terminal coil. All these MMP-2 models are subject to 20 ns molecular dynamics (MD) simulations followed by MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) calculations. The positioning of the N-terminal coil in the "superactivated" form is found to be energetically favored for the MMP-2 enzyme. Moreover, this configuration of the N-terminal moiety can facilitate the binding of peptide substrates. Globally, the results obtained in this study could be relevant for the structural-based design of specific MM...Continue Reading

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Citations

Feb 13, 2019·Journal of Biomolecular Structure & Dynamics·Cai YaoXianrong Qi
Sep 21, 2013·Journal of Computational Chemistry·Ernesto SuárezDimas Suárez
Aug 30, 2019·International Journal of Molecular Sciences·Leah Voit-OstrickiCharles R Watts
Feb 23, 2021·PLoS Computational Biology·Boris I RatnikovJeffrey W Smith
Jun 24, 2008·The Journal of Physical Chemistry. B·Natalia Díaz, Dimas Suárez
Jul 13, 2010·Journal of Chemical Theory and Computation·Haydee ValdésJuan Fernández-Recio
Nov 16, 2010·Journal of Chemical Theory and Computation·Jia ZhouH Bernhard Schlegel
Feb 14, 2012·The Journal of Physical Chemistry. B·Natalia Díaz, Dimas Suárez

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