The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study

Shah Md Abdur Rauf, Mohamed Ismael, Kamlesh Kumar Sahu, Ai Suzuki, Michihisa Koyama, Hideyuki Tsuboi, Nozomu Hatakeyama, Akira Endou, Hiromitsu Takaba, Carlos A. Del Carpio, Momoji Kubo, Akira Miyamoto

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R249S suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R249S affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation H168R on the R249S assists in maintaining the wild-type like flexibility of the L3 region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53.

元の言語英語
ページ(範囲)498-508
ページ数11
ジャーナルComputers in Biology and Medicine
40
発行部数5
DOI
出版物ステータス出版済み - 5 1 2010

Fingerprint

Genetic Suppression
DNA
Mutation
Tumor Suppressor Protein p53
Tumors
Hydrogen bonds
Proteins
Hydrogen
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Computer Science Applications
  • Health Informatics

これを引用

The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study. / Rauf, Shah Md Abdur; Ismael, Mohamed; Sahu, Kamlesh Kumar; Suzuki, Ai; Koyama, Michihisa; Tsuboi, Hideyuki; Hatakeyama, Nozomu; Endou, Akira; Takaba, Hiromitsu; Del Carpio, Carlos A.; Kubo, Momoji; Miyamoto, Akira.

:: Computers in Biology and Medicine, 巻 40, 番号 5, 01.05.2010, p. 498-508.

研究成果: ジャーナルへの寄稿記事

Rauf, SMA, Ismael, M, Sahu, KK, Suzuki, A, Koyama, M, Tsuboi, H, Hatakeyama, N, Endou, A, Takaba, H, Del Carpio, CA, Kubo, M & Miyamoto, A 2010, 'The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study', Computers in Biology and Medicine, 巻. 40, 番号 5, pp. 498-508. https://doi.org/10.1016/j.compbiomed.2010.03.004
Rauf, Shah Md Abdur ; Ismael, Mohamed ; Sahu, Kamlesh Kumar ; Suzuki, Ai ; Koyama, Michihisa ; Tsuboi, Hideyuki ; Hatakeyama, Nozomu ; Endou, Akira ; Takaba, Hiromitsu ; Del Carpio, Carlos A. ; Kubo, Momoji ; Miyamoto, Akira. / The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study. :: Computers in Biology and Medicine. 2010 ; 巻 40, 番号 5. pp. 498-508.
@article{fe3e0e0615044209bf622803c4f9390e,
title = "The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study",
abstract = "In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R249S suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R249S affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation H168R on the R249S assists in maintaining the wild-type like flexibility of the L3 region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53.",
author = "Rauf, {Shah Md Abdur} and Mohamed Ismael and Sahu, {Kamlesh Kumar} and Ai Suzuki and Michihisa Koyama and Hideyuki Tsuboi and Nozomu Hatakeyama and Akira Endou and Hiromitsu Takaba and {Del Carpio}, {Carlos A.} and Momoji Kubo and Akira Miyamoto",
year = "2010",
month = "5",
day = "1",
doi = "10.1016/j.compbiomed.2010.03.004",
language = "English",
volume = "40",
pages = "498--508",
journal = "Computers in Biology and Medicine",
issn = "0010-4825",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - The effect of R249S carcinogenic and H168R-R249S suppressor mutations on p53-DNA interaction, a multi scale computational study

AU - Rauf, Shah Md Abdur

AU - Ismael, Mohamed

AU - Sahu, Kamlesh Kumar

AU - Suzuki, Ai

AU - Koyama, Michihisa

AU - Tsuboi, Hideyuki

AU - Hatakeyama, Nozomu

AU - Endou, Akira

AU - Takaba, Hiromitsu

AU - Del Carpio, Carlos A.

AU - Kubo, Momoji

AU - Miyamoto, Akira

PY - 2010/5/1

Y1 - 2010/5/1

N2 - In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R249S suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R249S affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation H168R on the R249S assists in maintaining the wild-type like flexibility of the L3 region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53.

AB - In this study we have undertaken the theoretical analysis of the effect of R249S carcinogenic and H168R-R249S suppressor mutation at core domain of the tumor suppressor protein p53, on its natural interaction with DNA using a newly developed method. The results show that the carcinogenic mutation R249S affects the flexibility of L3 loop region in p53, inducing the loss of important hydrogen bonds observed at interaction in the wild-type with DNA, on the other hand the suppressor mutation H168R on the R249S assists in maintaining the wild-type like flexibility of the L3 region in p53 and thus recover the interaction terms lost in the carcinogenic mutation alone. The present study sets a new direction in the development of new drugs that may restore the interactions that lost as a consequence of the carcinogenic mutations in p53.

UR - http://www.scopus.com/inward/record.url?scp=77952552423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952552423&partnerID=8YFLogxK

U2 - 10.1016/j.compbiomed.2010.03.004

DO - 10.1016/j.compbiomed.2010.03.004

M3 - Article

C2 - 20403587

AN - SCOPUS:77952552423

VL - 40

SP - 498

EP - 508

JO - Computers in Biology and Medicine

JF - Computers in Biology and Medicine

SN - 0010-4825

IS - 5

ER -