The best of both worlds

2. December 2019

KIMMDY is born! A new simulation scheme combining Molecular Dynamics (MD) simulations with Kinetic Monte Carlo (KMC) enables bond scissions in all-atom simulations. The advantage of this hybrid approach over previous reactive simulation methods lies especially in its computational efficiency. Several orders of magnitude in timescales are bridged between the input sampling in MD and the reaction in the KMC step. This method developed at HITS has now been published inJournal of Chemical Theory and Computation“.

Proteins in their natural environment are exposed to various mechanical loads that might lead to covalent bond scissions even before macroscopic failure occurs. In regular Molecular Dynamics (MD) simulations, covalent bonds are predefined and chemical reactions cannot occur. Furthermore, such events rarely take place on timescales accessible with MD. Existing reactive approaches either rely on computationally expensive quantum calculations (e.g. QM/MM) or complex bond order formalisms in force fields (e.g. ReaxFF).

The new simulation scheme called KIMMDY (Kinetic Monte Carlo / Molecular Dynamics), developed from the Molecular Biomechanics group at HITS, can alleviate these issues through a hybrid combination of different simulation methods: bond rupture rates are calculated based on the interatomic distances in the MD simulation and then serve as an input for a Kinetic Monte Carlo step. This approach bridges the often apparent separation of accessible timescales.

Collagen-based materials, like the displayed achilles tendon, and other proteins are exposed to various mechanical loads that can lead to covalent bond scissions. In here, we present a new reactive and easily scalable hybrid Kinetic Monte Carlo / Molecular Dynamics (KIMMDY) scheme that enables bond scissions in all-atom MD simulations.

With this new technique bond ruptures in multi-million atom systems can now be investigated. Using KIMMDY it was shown that in tensed collagen, a structural protein of skin, bones and tendons, bond scissions clearly concentrate near the chemical crosslinks. After a (homolytic) bond breakage due to high tensile stress, highly reactive radicals are created in collagen. The subsequent created species could potentially act in signaling processes, converting mechanical forces into oxidative stress. Hence, this method opens up the path to further examine this biological highly relevant mechanism. It is also straightforwardly applicable to other complex (bio)materials under load and related chemistries.

The paper originated from the master thesis of scientist Benedikt Rennekamp at HITS and Heidelberg University. Since August 2019 he is PhD Student at HITS in the group of Frauke Gräter and a member of the Max Planck School «Matter to Life».

The most recent version of the software code is available online here.

Article in Journal of Chemical Theory and Computation:

Hybrid Kinetic Monte Carlo / Molecular Dynamics Simulations of Bond Scissions in Proteins
Benedikt Rennekamp, Fabian Kutzki, Agnieszka Obarska-Kosinska, Christopher Zapp, and Frauke Gräter
Journal of Chemical Theory and Computation
DOI: 10.1021/acs.jctc.9b00786

Scientific Contact:

Prof. Dr. Frauke Gräter
Group Leader „Molecular Biomechanics“
HITS – Heidelberg Institute for Theoretical Studies
E-mail: frauke.graeter@h-its.org

About HITS

The Heidelberg Institute for Theoretical Studies (HITS) was established in 2010 by the physicist and SAP co-founder Klaus Tschira (1940-2015) and the Klaus Tschira Foundation as a private, non-profit research institute. HITS conducts basic research in the natural sciences, mathematics and computer science, with a focus on the processing, structuring, and analyzing of large amounts of complex data and the development of computational methods and software. The research fields range from molecular biology to astrophysics. The shareholders of HITS are the HITS-Stiftung, which is a subsidiary of the Klaus Tschira Foundation, Heidelberg University and the Karlsruhe Institute of Technology (KIT). HITS also cooperates with other universities and research institutes and with industrial partners. The base funding of HITS is provided by the HITS Stiftung with funds received from the Klaus Tschira Foundation. The primary external funding agencies are the Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG), and the European Union.

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