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Anisotropic elastic network modeling of entire microtubules

Anisotropic elastic network modeling of entire microtubules
Anisotropic elastic network modeling of entire microtubules
Microtubules are supramolecular structures that make up the cytoskeleton and strongly affect the mechanical properties of the cell. Within the cytoskeleton filaments, the microtubule (MT) exhibits by far the highest bending stiffness. Bending stiffness depends on the mechanical properties and intermolecular interactions of the tubulin dimers (the MT building blocks). Computational molecular modeling has the potential for obtaining quantitative insights into this area. However, to our knowledge, standard molecular modeling techniques, such as molecular dynamics (MD) and normal mode analysis (NMA), are not yet able to simulate large molecular structures like the MTs; in fact, their possibilities are normally limited to much smaller protein complexes. In this work, we developed a multiscale approach by merging the modeling contribution from MD and NMA. In particular, MD simulations were used to refine the molecular conformation and arrangement of the tubulin dimers inside the MT lattice. Subsequently, NMA was used to investigate the vibrational properties of MTs modeled as an elastic network. The coarse-grain model here developed can describe systems of hundreds of interacting tubulin monomers (corresponding to up to 1,000,000 atoms). In particular, we were able to simulate coarse-grain models of entire MTs, with lengths up to 350 nm. A quantitative mechanical investigation was performed; from the bending and stretching modes, we estimated MT macroscopic properties such as bending stiffness, Young modulus, and persistence length, thus allowing a direct comparison with experimental data
0006-3495
2190-2199
Deriu, Marco A.
e9d0cab1-8b30-467f-9b8b-3e0b4276860f
Soncini, Monica
cc8bb1f6-7e09-4506-ac20-2f238b20cf2d
Orsi, Mario
62904259-9a93-4d02-8ce6-d8ef53dfcbf1
Patel, Mishal
62c3ca49-a0c7-483b-ae96-65ff410a9319
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Montevecchi, Franco M.
ad269be7-bcab-4220-a94b-c1fd2b02e980
Redaelli, Alberto
c8105735-c2c5-4f5f-8635-fa75bb9f9394
Deriu, Marco A.
e9d0cab1-8b30-467f-9b8b-3e0b4276860f
Soncini, Monica
cc8bb1f6-7e09-4506-ac20-2f238b20cf2d
Orsi, Mario
62904259-9a93-4d02-8ce6-d8ef53dfcbf1
Patel, Mishal
62c3ca49-a0c7-483b-ae96-65ff410a9319
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Montevecchi, Franco M.
ad269be7-bcab-4220-a94b-c1fd2b02e980
Redaelli, Alberto
c8105735-c2c5-4f5f-8635-fa75bb9f9394

Deriu, Marco A., Soncini, Monica, Orsi, Mario, Patel, Mishal, Essex, Jonathan W., Montevecchi, Franco M. and Redaelli, Alberto (2010) Anisotropic elastic network modeling of entire microtubules. Biophysical Journal, 99 (7), 2190-2199. (doi:10.1016/j.bpj.2010.06.070). (PMID:20923653)

Record type: Article

Abstract

Microtubules are supramolecular structures that make up the cytoskeleton and strongly affect the mechanical properties of the cell. Within the cytoskeleton filaments, the microtubule (MT) exhibits by far the highest bending stiffness. Bending stiffness depends on the mechanical properties and intermolecular interactions of the tubulin dimers (the MT building blocks). Computational molecular modeling has the potential for obtaining quantitative insights into this area. However, to our knowledge, standard molecular modeling techniques, such as molecular dynamics (MD) and normal mode analysis (NMA), are not yet able to simulate large molecular structures like the MTs; in fact, their possibilities are normally limited to much smaller protein complexes. In this work, we developed a multiscale approach by merging the modeling contribution from MD and NMA. In particular, MD simulations were used to refine the molecular conformation and arrangement of the tubulin dimers inside the MT lattice. Subsequently, NMA was used to investigate the vibrational properties of MTs modeled as an elastic network. The coarse-grain model here developed can describe systems of hundreds of interacting tubulin monomers (corresponding to up to 1,000,000 atoms). In particular, we were able to simulate coarse-grain models of entire MTs, with lengths up to 350 nm. A quantitative mechanical investigation was performed; from the bending and stretching modes, we estimated MT macroscopic properties such as bending stiffness, Young modulus, and persistence length, thus allowing a direct comparison with experimental data

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Published date: October 2010

Identifiers

Local EPrints ID: 179871
URI: http://eprints.soton.ac.uk/id/eprint/179871
ISSN: 0006-3495
PURE UUID: 28fd2344-ac0c-40e4-a367-2ac257a383eb
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

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Date deposited: 04 Apr 2011 14:26
Last modified: 10 Dec 2019 01:55

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