A collective motion description of tubulin βT7 loop dynamics
Tubulin is a hetero-dimeric protein that polymerizes into microtubules and facilitates, among other things, eukaryotic cell division. Thus, any agent that interferes with tubulin polymerization is of therapeutic interest, vis-à-vis cancer. For example, colchicine is known to prevent tubulin polymeri...
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doaj-020d3515285e41acb921ab4eefbcf5312020-11-25T02:58:41ZengThe Biophysical Society of JapanBiophysics and Physicobiology2189-47792019-11-011610.2142/biophysico.16.0_264A collective motion description of tubulin βT7 loop dynamicsSarbani Chattopadhyaya0Debamitra Chakravorty1Gautam Basu2Department of Biophysics, Bose Institute, VIIM, Kolkata 700054, IndiaDepartment of Biophysics, Bose Institute, VIIM, Kolkata 700054, IndiaDepartment of Biophysics, Bose Institute, VIIM, Kolkata 700054, IndiaTubulin is a hetero-dimeric protein that polymerizes into microtubules and facilitates, among other things, eukaryotic cell division. Thus, any agent that interferes with tubulin polymerization is of therapeutic interest, vis-à-vis cancer. For example, colchicine is known to prevent tubulin polymerization by binding at the heterodimeric interface of αβ-tubulin. Crystal structures of tubulin bound to colchicine have shown that the dynamical conformation of a loop (βT7) plays an important role in colchicine binding. The βT7 loop dynamics also plays an important role in yielding curved versus straight αβ-tubulin dimers, only the latter being compatible with the microtubule assembly. Understanding the molecular mechanism of inhibition of microtubule assembly can lead to development of better therapeutic agents. In this work we were able to capture the βT7 loop flip by performing 200 ns molecular dynamics simulation of ligand-free αβ-tubulins. The loop flip could be described by only two independent collective vectors, obtained from principal component analysis. The first vector describes the flip while the second vector describes the trigger. The collective variables identified in this work is a natural reaction coordinate for functionally important tubulin dynamics, which allowed us to describe in detail the interaction network associated with the flip and the overall straight/curved conformational equilibrium.https://doi.org/10.2142/biophysico.16.0_264tubulin loop dynamicscolchicine binding sitecollective motionβt7 loop flip |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarbani Chattopadhyaya Debamitra Chakravorty Gautam Basu |
spellingShingle |
Sarbani Chattopadhyaya Debamitra Chakravorty Gautam Basu A collective motion description of tubulin βT7 loop dynamics Biophysics and Physicobiology tubulin loop dynamics colchicine binding site collective motion βt7 loop flip |
author_facet |
Sarbani Chattopadhyaya Debamitra Chakravorty Gautam Basu |
author_sort |
Sarbani Chattopadhyaya |
title |
A collective motion description of tubulin βT7 loop dynamics |
title_short |
A collective motion description of tubulin βT7 loop dynamics |
title_full |
A collective motion description of tubulin βT7 loop dynamics |
title_fullStr |
A collective motion description of tubulin βT7 loop dynamics |
title_full_unstemmed |
A collective motion description of tubulin βT7 loop dynamics |
title_sort |
collective motion description of tubulin βt7 loop dynamics |
publisher |
The Biophysical Society of Japan |
series |
Biophysics and Physicobiology |
issn |
2189-4779 |
publishDate |
2019-11-01 |
description |
Tubulin is a hetero-dimeric protein that polymerizes into microtubules and facilitates, among other things, eukaryotic cell division. Thus, any agent that interferes with tubulin polymerization is of therapeutic interest, vis-à-vis cancer. For example, colchicine is known to prevent tubulin polymerization by binding at the heterodimeric interface of αβ-tubulin. Crystal structures of tubulin bound to colchicine have shown that the dynamical conformation of a loop (βT7) plays an important role in colchicine binding. The βT7 loop dynamics also plays an important role in yielding curved versus straight αβ-tubulin dimers, only the latter being compatible with the microtubule assembly. Understanding the molecular mechanism of inhibition of microtubule assembly can lead to development of better therapeutic agents. In this work we were able to capture the βT7 loop flip by performing 200 ns molecular dynamics simulation of ligand-free αβ-tubulins. The loop flip could be described by only two independent collective vectors, obtained from principal component analysis. The first vector describes the flip while the second vector describes the trigger. The collective variables identified in this work is a natural reaction coordinate for functionally important tubulin dynamics, which allowed us to describe in detail the interaction network associated with the flip and the overall straight/curved conformational equilibrium. |
topic |
tubulin loop dynamics colchicine binding site collective motion βt7 loop flip |
url |
https://doi.org/10.2142/biophysico.16.0_264 |
work_keys_str_mv |
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