This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.106.089987v1 92/2/394    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Drabik, P. Articles by Kovalenko, A. Search for Related Content PubMed PubMed Citation Articles by Drabik, P. Articles by Kovalenko, A.

Microtubule Stability Studied by Three-Dimensional Molecular Theory of Solvation

Piotr Drabik ^*, Sergey Gusarov ^* and Andriy Kovalenko ^* 

^* National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta, Canada; and Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada

Correspondence: Address reprint requests to Andriy Kovalenko, National Institute for Nanotechnology, 11421 Saskatchewan Dr., Edmonton, AB T6G 2M9, Canada. E-mail: andriy.kovalenko{at}nrc-cnrc.gc.ca.

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 ß-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.

This article has been cited by other articles:

				T. Yamazaki, N. Blinov, D. Wishart, and A. Kovalenko Hydration Effects on the HET-s Prion and Amyloid-{beta} Fibrillous Aggregates, Studied with Three-Dimensional Molecular Theory of Solvation Biophys. J., November 15, 2008; 95(10): 4540 - 4548. [Abstract] [Full Text] [PDF]

				R. I. Dima and H. Joshi Probing the origin of tubulin rigidity with molecular simulations PNAS, October 14, 2008; 105(41): 15743 - 15748. [Abstract] [Full Text] [PDF]

				V. Hunyadi and I. M. Janosi Metastability of Microtubules Induced by Competing Internal Forces Biophys. J., May 1, 2007; 92(9): 3092 - 3097. [Abstract] [Full Text] [PDF]