The influence of water potential in simulation: a catabolite activator protein case study

Steven Y Liem,Paul L A Popelier

doi:10.1007/s00894-019-4095-3

Abstract

We present a rare comparison of structures of the same protein but generated by different potentials. We used four popular water potentials (SPC, TIP3P, TIP4P, TIP5P) in conjunction with the equally popular ff99SB. However, the ff12SB protein potential was used with TI3P only. Simulations (60 ns) were run on the catabolite activator protein (CAP), which is a textbook case of allosteric interaction. Overall, all potentials generated largely similar structures but failed to reproduce a crucial structural feature determined by NMR experiment. This example shows the need to develop next-generation potentials.Graphical abstractCatabolite activator protein

Highlights

Molecular simulation has become the third way of doing science, next to theory and experiment
The averaged densities and energetics of the systems are reasonably similar indicating that all potentials produce realistic system densities. This result should not be taken for granted because it is quite remarkable that the addition of catabolite activator protein (CAP) to an originally pure liquid water system largely preserves the latter’s density
The only exception is for TIP3P when used in conjunction with ff12SB, where the diffusion coefficient is slightly reduced

Summary

Introduction

Molecular simulation has become the third way of doing science, next to theory and experiment. Powerful computers and algorithms provide a stream of information, independent from experiment, which sheds light on challenging biological systems and problems. Allostery is one such crucial and ubiquitous biochemical phenomenon, which consists of a triggering event at one site of a macromolecule leading to a corresponding effect at a distal site. For this phenomenon to be understood it is essential that experiment and simulation converge to the same view. Experiment tends to rely more and more on models and simulation in order to extract from its measured signals the desired structure, mechanism, and explanation of a

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