Water model determines thermosensitive and physicochemical properties of poly(N-isopropylacrylamide) in molecular simulations

Abstract

Poly (N-isopropylacrylamide) (PNIPAM) is a famous representative of thermosensitive polymers. Thermosensitive polymers undergo a phase transition with lower critical solution temperature. Commonly, their phase behavior is linked to a conformational collapse above a certain temperature. This thermosensitive conformational transition is called Coil-Globule transition. In contrast, most other polymers usually show inverse temperature behavior, i.e., an upper critical solution temperature, corresponding to a Globule-Coil transition. Besides their numerous possible applications, thermosensitive polymers are of interest for fundamental research, because of similarities to macromolecular conformational transitions, e.g., protein folding. The counter-intuitive behavior of thermosensitive polymers is commonly associated with solvation effects. Thus, an accurate description of the solvent is crucial for the investigation of thermosensitive polymers in molecular simulations. Here, we investigate the influence of the in silico water model on the thermosensitive Coil-Globule transition in molecular dynamics simulations. To this end, we performed extensive atomistic simulations of the syndiotactic PNIPAM 20-mer at multiple temperatures with eight different water models–four of which are 3-point water models (TIP3P-type) and four are 4-point water models (TIP4P-type). We found that the thermosensitive Coil-Globule transition is strongly influenced by the water model in the simulations. Depending on the water model, the conformational ensemble of the polymer is shifted significantly, which leads to dramatically different results: The estimated transition temperature may span between 255 and 350 K. Consequently, depending on the description of the solvent, the physicochemical and mechanical properties of these polymers, e.g., the polymer-solvent affinity and persistence length, vary. These divergent results originate from the strength of interactions between polymer and solvent, but also on the bulk state of the solvent. Both these quantities vary between water models. We found that the Lennard-Jones interaction parameter ϵ of the water model correlates with the transition temperature of the polymer. Indeed, the quadrupole moment of the water model shows an even higher correlation with this quantity. Our results suggest a connection between the phase diagram of the solvent and the thermosensitive transition of the polymer.

The Role of Force Fields and Water Models in Protein Folding and Unfolding Dynamics

“…This choice also plays an important role in the estimation of properties that are relevant for experimental studies. We have recently shown that the choice of the water model in molecular simulations may have a dramatic effect on the thermodynamics of complex conformational transitions, such as the Coil–Globule transition, which shares similarities with protein folding . Such biased ensembles will influence the calculated ensemble properties.…”

“…We have recently shown that the choice of the water model in molecular simulations may have a dramatic effect on the thermodynamics of complex conformational transitions, such as the Coil–Globule transition, which shares similarities with protein folding. 108 Such biased ensembles will influence the calculated ensemble properties. For example, in structure refinement protocols, force fields and their respective water models are often used to optimize the final conformations based on experimental measures.…”

Liquid–Vapor Coexistence and Spontaneous Evaporation at Atmospheric Pressure of Common Rigid Three-Point Water Models in Molecular Simulations

“…However, frequently, realistic simulations at higher temperatures are also desired. This concerns, for example, temperature-dependent processes such as protein denaturation or conformational transitions of thermoresponsive polymers. − The choice of water model may influence such temperature-dependent processes in molecular simulations tremendously. − In simulations at elevated temperatures, it is important to be sure that the water model of choice is still in the liquid phase. Furthermore, exploring the correlation between the temperature-dependent properties of in silico water and the parameters of different existing models (such as geometry and charge distribution) is of interest.…”

“… 35 − 39 The choice of water model may influence such temperature-dependent processes in molecular simulations tremendously. 40 − 42 In simulations at elevated temperatures, it is important to be sure that the water model of choice is still in the liquid phase. Furthermore, exploring the correlation between the temperature-dependent properties of in silico water and the parameters of different existing models (such as geometry and charge distribution) is of interest.…”