Toward Temperature-Dependent Coarse-Grained Potentials of Side-Chain Interactions for Protein Folding Simulations. II. Molecular Dynamics Study of Pairs of Different Types of Interactions in Water at Various Temperatures

By means of molecular dynamics simulations of 15 pairs of molecules selected to model the interactions of nonpolar, nonpolar and polar, nonpolar and charged, polar, and polar and charged side chains in water, we determined the potentials of mean force (PMFs) of pairs of interacting molecules in water as functions of distance between the interacting particles or their distance and orientations at three temperatures: 283, 323, and 373 K, respectively. The systems were found to fall into the following four categories as far as the temperature dependence of the PMF is concerned: (i) pairs for which association is entropy-driven, (ii) pairs for which association is energy-driven, (iii) pairs of positively charged solute molecules, for which association is energy-driven with unfavorable entropy change, and (iv) the remaining systems for which temperature dependence is weak. For each pair of PMFs, entropic and energetic contributions have been discussed

Theoretical Studies of Interactions between O‑Phosphorylated and Standard Amino-Acid Side-Chain Models in Water

Phosphorylation is a common post-translational modification of the amino-acid side chains (serine, tyrosine, and threonine) that contain hydroxyl groups. The transfer of the negatively charged phosphate group from an ATP molecule to such amino-acid side chains leads to changes in the local conformations of proteins and the pattern of interactions with other amino-acid side-chains. A convenient characteristic of the side chain–side chain interactions in the context of an aqueous environment is the potential of mean force (PMF) in water. A series of umbrella-sampling molecular dynamic (MD) simulations with the AMBER force field were carried out for pairs of O-phosphorylated serine (pSer), threonine (pThr), and tyrosine, (pTyr) with natural amino acids in a TIP3P water model as a solvent at 298 K. The weighted-histogram analysis method was used to calculate the four-dimensional potentials of mean force. The results demonstrate that the positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the relative orientation depend on the character of the interacting pairs. More distinct minima are observed for oppositely charged pairs such as, e.g., O-phosphorylated side-chains and positively charged ones, such as the side-chains of lysine and arginine