Statistical Thermodynamics for Binding of an RNA Aptamer and a Partial Peptide of a Prion Protein

Abstract

It has been reported that a novel RNA aptamer with 12 residues (R12) binds to a partial peptide of a prion protein (P16) [1]. This binding is expected to prevent prion diseases, but its driving force remains rather unclear. Here we calculate the free-energy change upon the binding of R12 and P16 using molecular mechanics, the three-dimensional (3D) reference interaction site model (RISM) theory [2], and the hybrid method in which the angle-dependent integral equation theory [3] applied to a multipolar water model [4] is combined with the morphometric approach [5]. The 3D-RISM theory and the hybrid method are employed for calculating the hydration energy and the hydration entropy, respectively. We show that the large decrease in the intermolecular energy upon the binding is almost cancelled out by a correspondingly large increase in the hydration energy. The binding is driven by a large gain in the translational, configurational entropy of water originating primarily from the reduction in water crowding in the system. Our physical picture of the binding can be described as follows: The binding, which is driven by the water-entropy effect, accompanies a loss of R12-water and P16-water electrostatic attractive and van der Waals interactions. But the loss is compensated by a gain in R12-P16 electrostatic attractive and van der Waals interactions.[1] T. Mashima, et al., Nucleic Acids Res. 41, 1355 (2013).[2] T. Imai, et al., J. Chem. Phys. 126, 225102 (2007).[3] M. Kinoshita, J. Chem. Phys. 128, 0245071 (2008).[4] P. G. Kusalik and G. N. Patey, Mol. Phys. 65, 1105 (1988).[5] R. Roth, Y. Harano, and M. Kinoshita, Phys. Rev. Lett. 97, 078101 (2006).