Adaptive Resolution Simulation of Supramolecular Water: The Concurrent Making, Breaking, and Remaking of Water Bundles

The adaptive resolution scheme (AdResS) is a multiscale molecular dynamics simulation approach that can concurrently couple atomistic (AT) and coarse-grained (CG) resolution regions, i.e., the molecules can freely adapt their resolution according to their current position in the system. Coupling to supramolecular CG models, where several molecules are represented as a single CG bead, is challenging, but it provides higher computational gains and connection to the established MARTINI CG force field. Difficulties that arise from such coupling have been so far bypassed with bundled AT water models, where additional harmonic bonds between oxygen atoms within a given supramolecular water bundle are introduced. While these models simplify the supramolecular coupling, they also cause in certain situations spurious artifacts, such as partial unfolding of biomolecules. In this work, we present a new clustering algorithm SWINGER that can concurrently make, break, and remake water bundles and in conjunction with the AdResS permits the use of original AT water models. We apply our approach to simulate a hybrid SPC/MARTINI water system and show that the essential properties of water are correctly reproduced with respect to the standard monoscale simulations. The developed hybrid water model can be used in biomolecular simulations, where a significant speed up can be obtained without compromising the accuracy of the AT water model

ENZO URL:

<p><a href="http://enzo.cmm.ki.si" target="_blank">http://enzo.cmm.ki.si</a><b>.</b> The ENZO web page provides a short introduction and links to a quick guide, examples and ENZO tool.</p

Michaelis-Menten reaction scheme.

<p>E is the free enzyme, S the substrate, ES the Michaelis complex and P the product; <i>k₀</i> is a second order and <i>k₁</i> and <i>k₂</i> are first order rate constants, respectively. The differential equations were automatically generated from the drawn reaction scheme by ENZO.</p

Converged results of parameter fitting for enzyme active site titration experiment.

<p>Initial concentrations of enzyme E and inhibitor I for progress curve files tfk1.dat, tfk2.dat, tfk3.dat (<i>Experimental Data</i> panel shows tfk1.dat) are fitted in the interval of [0, 10²⁰]; the initial concentration of EI is zero and fixed; the checkbox “E” is checked under <i>Measured Species</i>, which signifies that E is the measured quantity and the progress curves below represent the time course of its residual activity. The respective units of the residual activity in the Y-axis are OD/min and the units of time in X-axis are seconds. Fitted rate constant <i>k₀</i> and initial values of E and I at three different concentrations of I are displayed under the <i>Evaluated Parameters</i> in the upper right corner panel, the experimental progress curves are blue and the fitted curves are red as shown in <i>Time Course of the Reaction</i> chart at the bottom panel of the screen. The arrows mark the difference between the inital value and the plateau.</p