We study microtubular supramolecular architectures of tubulin dimers self-assembling into linear protofilaments, in turn forming a closed tube, which is an important component of the cytoskeleton. We identify the protofilament arrangements with the lowest free energy using molecular dynamics to optimize tubulin conformations. We then use the three-dimensional molecular theory of solvation to obtain the hydration structure of protofilaments built of optimized tubulins and the solvent-mediated effective potential between them. The latter theoretical method, based on first principles of statistical mechanics, is capable of predicting the structure and thermodynamics of solvation of supramolecular architectures. We obtained a set of profiles of the potential of mean force between protofilaments in a periodic two-dimensional sheet in aqueous solution. The profiles were calculated for a number of amino acid sequences, tubulin conformations, and spatial arrangements of protofilaments. The results indicate that the effective interaction between protofilaments in aqueous solution depends little on the isotypes studied; however, it strongly depends on the M loop conformation of beta-tubulin. Based on the analysis of the potential of mean force between adjacent protofilaments, we found the optimal arrangement of protofilaments, which is in good agreement with other studies. We also decomposed the potential of mean force into its energetic and entropic components, and found that both are considerable in the free-energy balance for the stabilized protofilament arrangements.