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...

Full description

Bibliographic Details
Main Authors: Sarbani Chattopadhyaya, Debamitra Chakravorty, Gautam Basu
Format: Article
Language:English
Published: The Biophysical Society of Japan 2019-11-01
Series:Biophysics and Physicobiology
Subjects:
Online Access:https://doi.org/10.2142/biophysico.16.0_264
id doaj-020d3515285e41acb921ab4eefbcf531
record_format Article
spelling 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 AT sarbanichattopadhyaya acollectivemotiondescriptionoftubulinbt7loopdynamics
AT debamitrachakravorty acollectivemotiondescriptionoftubulinbt7loopdynamics
AT gautambasu acollectivemotiondescriptionoftubulinbt7loopdynamics
AT sarbanichattopadhyaya collectivemotiondescriptionoftubulinbt7loopdynamics
AT debamitrachakravorty collectivemotiondescriptionoftubulinbt7loopdynamics
AT gautambasu collectivemotiondescriptionoftubulinbt7loopdynamics
_version_ 1724705603423567872