Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin

Travis J. A. Craddock; Jack A. Tuszynski; Jonathan Y. Mane; Khaled Barakat; Chih-Yuan Tseng; Melissa Gajewski; Philip Winter; Laleh Alisaraie; Jordan Patterson; Eric Carpenter; Weiwei Wang; Michael K. Deyholos; Linji Li; Xiao Sun; Yong Zhang; Gane Ka-Shu Wong

doi:10.1007/s11095-012-0829-y

Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin

Travis J. A. Craddock
, Jack A. Tuszynski
, Jonathan Y. Mane
, Khaled Barakat
, Chih-Yuan Tseng
, Melissa Gajewski
, Philip Winter
, Laleh Alisaraie
, Jordan Patterson
, Eric Carpenter
, Weiwei Wang
, Michael K. Deyholos
, Linji Li
, Xiao Sun
, Yong Zhang
, Gane Ka-Shu Wong

College of Psychology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

<p> <h3> Purpose </h3></p><p> To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel’s cytotoxic action. <h3> Methods </h3></p><p> Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity <em> de novo </em> assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson–Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences. <h3> Results </h3></p><p> We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel. <h3> Conclusions </h3></p><p> The yew has achieved a significant reduction of paclitaxel’s affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel.</p>

Original language	American English
Journal	Pharmaceutical Research
Volume	29
DOIs	https://doi.org/10.1007/s11095-012-0829-y
State	Published - Nov 1 2012

Keywords

Chemotherapy
Nanopores
Paclitaxel
Tubulin
Yew Tree

Disciplines

Psychology

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http://link.springer.com/article/10.1007/s11095-012-0829-y

Cite this

Craddock, T. J. A., Tuszynski, J. A., Mane, J. Y., Barakat, K., Tseng, C.-Y., Gajewski, M., Winter, P., Alisaraie, L., Patterson, J., Carpenter, E., Wang, W., Deyholos, M. K., Li, L., Sun, X., Zhang, Y., & Wong, G. K.-S. (2012). Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin. Pharmaceutical Research, 29. https://doi.org/10.1007/s11095-012-0829-y

Craddock, TJA, Tuszynski, JA, Mane, JY, Barakat, K, Tseng, C-Y, Gajewski, M, Winter, P, Alisaraie, L, Patterson, J, Carpenter, E, Wang, W, Deyholos, MK, Li, L, Sun, X, Zhang, Y & Wong, GK-S 2012, 'Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin', Pharmaceutical Research, vol. 29. https://doi.org/10.1007/s11095-012-0829-y

@article{4a208094f9f74d12a192d2418443d47c,

title = "Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin",

abstract = " Purpose To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel\’s cytotoxic action. Methods Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity de novo assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson\–Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences. Results We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel. Conclusions The yew has achieved a significant reduction of paclitaxel\’s affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel.",

keywords = "Chemotherapy, Nanopores, Paclitaxel, Tubulin, Yew Tree",

author = "Craddock, \{Travis J. A.\} and Tuszynski, \{Jack A.\} and Mane, \{Jonathan Y.\} and Khaled Barakat and Chih-Yuan Tseng and Melissa Gajewski and Philip Winter and Laleh Alisaraie and Jordan Patterson and Eric Carpenter and Weiwei Wang and Deyholos, \{Michael K.\} and Linji Li and Xiao Sun and Yong Zhang and Wong, \{Gane Ka-Shu\}",

year = "2012",

month = nov,

day = "1",

doi = "10.1007/s11095-012-0829-y",

language = "American English",

volume = "29",

journal = "Pharmaceutical Research",

issn = "0724-8741",

publisher = "Springer",

}

TY - JOUR

T1 - Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin

AU - Craddock, Travis J. A.

AU - Tuszynski, Jack A.

AU - Mane, Jonathan Y.

AU - Barakat, Khaled

AU - Tseng, Chih-Yuan

AU - Gajewski, Melissa

AU - Winter, Philip

AU - Alisaraie, Laleh

AU - Patterson, Jordan

AU - Carpenter, Eric

AU - Wang, Weiwei

AU - Deyholos, Michael K.

AU - Li, Linji

AU - Sun, Xiao

AU - Zhang, Yong

AU - Wong, Gane Ka-Shu

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Purpose To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel’s cytotoxic action. Methods Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity de novo assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson–Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences. Results We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel. Conclusions The yew has achieved a significant reduction of paclitaxel’s affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel.

AB - Purpose To explore possible ways in which yew tree tubulin is naturally resistant to paclitaxel. While the yew produces a potent cytotoxin, paclitaxel, it is immune to paclitaxel’s cytotoxic action. Methods Tubulin sequence data for plant species were obtained from Alberta 1000 Plants Initiative. Sequences were assembled with Trinity de novo assembly program and tubulin identified. Homology modeling using MODELLER software was done to generate structures for yew tubulin. Molecular dynamics simulations and molecular mechanics Poisson–Boltzmann calculations were performed with the Amber package to determine binding affinity of paclitaxel to yew tubulin. ClustalW2 program and PHYLIP package were used to perform phylogenetic analysis on plant tubulin sequences. Results We specifically analyzed several important regions in tubulin structure: the high-affinity paclitaxel binding site, as well as the intermediate binding site and microtubule nanopores. Our analysis indicates that the high-affinity binding site contains several substitutions compared to human tubulin, all of which reduce the binding energy of paclitaxel. Conclusions The yew has achieved a significant reduction of paclitaxel’s affinity for its tubulin by utilizing several specific residue changes in the binding pocket for paclitaxel.

KW - Chemotherapy

KW - Nanopores

KW - Paclitaxel

KW - Tubulin

KW - Yew Tree

UR - https://nsuworks.nova.edu/cps_facarticles/579

UR - http://link.springer.com/article/10.1007/s11095-012-0829-y

U2 - 10.1007/s11095-012-0829-y

DO - 10.1007/s11095-012-0829-y

M3 - Article

SN - 0724-8741

VL - 29

JO - Pharmaceutical Research

JF - Pharmaceutical Research

ER -

Modeling the Yew Tree Tubulin and a Comparison of its Interaction with Paclitaxel to Human Tubulin

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