ビタミンD受容体とキラリティが異なるリガンド間の特異的相互作用: ab initioフラグメント分子軌道計算
ビタミンD受容体（VDR）とキラリティーが異なる2種類のリガンド間の結合親和性が実験により解析され、リガンドのキラリティーの違いにより、VDRへの結合親和性が大きく変化することが見出された。この原因を明らかにするため、VDRと2種類のリガンド間の特異的相互作用を、ab initio フラグメント分子軌道（FMO）計算を用いて調べた。 その結果、リガンド中でキラリティーが異なる部位が、VDRのヒスチジン残基側鎖のイミダゾール環と強く相互作用し、VDRとリガンド間の結合特性性がヒスチジンのプロトン化状態に依存することが明らかになった。...
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| Published in | Chem-Bio Informatics Journal Vol. 18; pp. 32 - 43 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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情報計算化学生物学会(CBI学会)
2018
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| ISSN | 1347-6297 1347-0442 |
| DOI | 10.1273/cbij.18.32 |
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| Abstract | ビタミンD受容体（VDR）とキラリティーが異なる2種類のリガンド間の結合親和性が実験により解析され、リガンドのキラリティーの違いにより、VDRへの結合親和性が大きく変化することが見出された。この原因を明らかにするため、VDRと2種類のリガンド間の特異的相互作用を、ab initio フラグメント分子軌道（FMO）計算を用いて調べた。 その結果、リガンド中でキラリティーが異なる部位が、VDRのヒスチジン残基側鎖のイミダゾール環と強く相互作用し、VDRとリガンド間の結合特性性がヒスチジンのプロトン化状態に依存することが明らかになった。 |
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| AbstractList | ビタミンD受容体（VDR）とキラリティーが異なる2種類のリガンド間の結合親和性が実験により解析され、リガンドのキラリティーの違いにより、VDRへの結合親和性が大きく変化することが見出された。この原因を明らかにするため、VDRと2種類のリガンド間の特異的相互作用を、ab initio フラグメント分子軌道（FMO）計算を用いて調べた。 その結果、リガンド中でキラリティーが異なる部位が、VDRのヒスチジン残基側鎖のイミダゾール環と強く相互作用し、VDRとリガンド間の結合特性性がヒスチジンのプロトン化状態に依存することが明らかになった。 |
| Author | 武田, 涼介 小林, 一徹 栗田, 典之 橘高, 敦史 鈴木, 理恵 上村, みどり 河合, 健太郎 |
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| References | [2] Walters, M. R. Newly identified actions of the vitamin D endocrine system. Endocr. Rev. 1992, 13, 719-764. [7] Kitaura, K.; Ikeo, E.; Asada, T.; Nakano, T.; Uebayashi, M. Fragment molecular orbital method: an approximate computational method for large molecules. Chem. Phys. Lett. 1999, 313 (3-4), 701-706. [24] Tsukamoto, T.; Kato, K.; Kato, A.; Nakano, T.; Mochizuki, Y.; Fukuzawa, K. Implementation of pair interaction energy decomposition analysis and its applications to protein-ligand systems. J. Comp. Chem. Jpn. 2015, 14, 1-9. [6] Takeda, R.; Kobayashi, I.; Shimamura, K.; Ishimura, H.; Kadoya, R.; et al. Specific interactions between vitamin-D receptor and its ligands: ab initio molecular orbital calculations in water. J. Steroid Biochem. Mol. Biol. 2017, 171, 75-79. [11] Matsuo, M.; Hasegawa, A.; Takano, M.; Saito, H.; Kakuda, S.; et al. Synthesis of 2α-Heteroarylalkyl active vitamin D3 with therapeutic effect on enhancing bone mineral density in vivo. ACS Med. Chem. Lett. 2013, 4, 671-674. [3] Kàllay, E.; Bareis, P.; Bajna, E.; Kriwanek, S.; Bonner, E.; et al. Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress. Food Chem. Toxicol. 2002, 40, 1191-1196. [23] Fedorov, D. G.; Kitaura, K. Pair interaction energy decomposition analysis. J. Comput. Chem. 2007, 28, 222-237. [8] FMO Drug Design Consortium. http://eniac.scitec.kobe-u.ac.jp/fmodd [5] Hourai, S.; Rodrigues, L. C.; Antony, P.; Reina-San-Martin, B.; Ciesielski, F.; et al. Structure-based design of a superagonist ligand for the vitamin D nuclear receptor. Chem. Biol. 2008, 15, 383-392. [4] Deeb, K. K.; Trump, D. L.; Johnson, C. S. Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat. Rev. Cancer 2007, 7, 684-700. [10] Cornell, W. D.; Cieplak, P.; Bayly, C. I.; et al. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197. [13] Søndergaard, C. R.; Olsson, M. H. M.; Rostkowski, M.; Jensen, J. H. Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa Values. J. Chem. Theory Comput. 2011, 7, 2284-2295. [21] Mochizuki, Y.; Yamashita, K.; Nakano, T.; Okiyama, Y.; Fukuzawa, K.; et al. Higher-order correlated calculations based on fragment molecular orbital scheme. Theor. Chem. Acc. 2011, 130, 515-530. [12] Rochel, N.; Wurtz, J. M.; Mitschler, A.; Klaholz, B.; Moras, D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 2000, 5, 173-179. [1] Odrzywolska, M.; Chodyn´ski, M.; Zorgdrager, J.; Velde, Jan-Paul, V. D.; Kutner, A. Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol. Chirality 1999, 11, 701-706. [17] Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926-935. [15] Case, D. A.; et al. AMBER 12. University of California, San Francisco, 2012. [18] Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general amber force field. J. Comput. Chem. 2004, 25, 1157-1174. [14] Olsson, M. H. M.; Søndergaard, C. R.; Rostkowski, M.; Jensen, J. H. PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J. Chem. Theory Comput. 2011, 7, 525-537. [16] Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins: Structure, Function, and Bioinformatics 2010, 78, 1950-1958. [22] Fukuzawa, K.; Nakano, T.; Kato, A.; Mochizuki, Y.; Tanaka, S. Applications of the fragment molecular orbital method for bio-macromolecules. J. Comp. Chem. Jpn. 2007, 6, 185-198. [9] Frisch M. J.; et al. Gaussian09. Revision A.02, Gaussian, Inc., Wallingford, CT, 2009. [19] Mochizuki, Y.; Nakano, T.; Koikegami, S.; Tanimori, S.; Abe, Y.; et al. A parallelized integral-direct second-order Møller-Plesset perturbation theory method with a fragment molecular orbital scheme. Theor. Chem. Acc. 2004, 112, 442-452. [25] Yamagishi, K.; Tokiwa, H.; Makishima, M.; Yamada, S. Interactions between 1α,25(OH)2D3 and residues in the ligand-binding pocket of the vitamin D receptor: A correlated fragment molecular orbital study. J. Steroid Biochem. Mol. Biol. 2010, 121, 63-67. [20] Mochizuki, Y.; Koikegami, S.; Nakano, T.; Amari, S.; Kitaura, K. Large scale MP2 calculations with fragment molecular orbital scheme. Chem. Phys. Lett. 2004, 396, 473-479. |
| References_xml | – reference: [1] Odrzywolska, M.; Chodyn´ski, M.; Zorgdrager, J.; Velde, Jan-Paul, V. D.; Kutner, A. Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol. Chirality 1999, 11, 701-706. – reference: [6] Takeda, R.; Kobayashi, I.; Shimamura, K.; Ishimura, H.; Kadoya, R.; et al. Specific interactions between vitamin-D receptor and its ligands: ab initio molecular orbital calculations in water. J. Steroid Biochem. Mol. Biol. 2017, 171, 75-79. – reference: [2] Walters, M. R. Newly identified actions of the vitamin D endocrine system. Endocr. Rev. 1992, 13, 719-764. – reference: [7] Kitaura, K.; Ikeo, E.; Asada, T.; Nakano, T.; Uebayashi, M. Fragment molecular orbital method: an approximate computational method for large molecules. Chem. Phys. Lett. 1999, 313 (3-4), 701-706. – reference: [8] FMO Drug Design Consortium. http://eniac.scitec.kobe-u.ac.jp/fmodd/ – reference: [23] Fedorov, D. G.; Kitaura, K. Pair interaction energy decomposition analysis. J. Comput. Chem. 2007, 28, 222-237. – reference: [24] Tsukamoto, T.; Kato, K.; Kato, A.; Nakano, T.; Mochizuki, Y.; Fukuzawa, K. Implementation of pair interaction energy decomposition analysis and its applications to protein-ligand systems. J. Comp. Chem. Jpn. 2015, 14, 1-9. – reference: [13] Søndergaard, C. R.; Olsson, M. H. M.; Rostkowski, M.; Jensen, J. H. Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa Values. J. Chem. Theory Comput. 2011, 7, 2284-2295. – reference: [5] Hourai, S.; Rodrigues, L. C.; Antony, P.; Reina-San-Martin, B.; Ciesielski, F.; et al. Structure-based design of a superagonist ligand for the vitamin D nuclear receptor. Chem. Biol. 2008, 15, 383-392. – reference: [18] Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general amber force field. J. Comput. Chem. 2004, 25, 1157-1174. – reference: [25] Yamagishi, K.; Tokiwa, H.; Makishima, M.; Yamada, S. Interactions between 1α,25(OH)2D3 and residues in the ligand-binding pocket of the vitamin D receptor: A correlated fragment molecular orbital study. J. Steroid Biochem. Mol. Biol. 2010, 121, 63-67. – reference: [14] Olsson, M. H. M.; Søndergaard, C. R.; Rostkowski, M.; Jensen, J. H. PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J. Chem. Theory Comput. 2011, 7, 525-537. – reference: [16] Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins: Structure, Function, and Bioinformatics 2010, 78, 1950-1958. – reference: [17] Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926-935. – reference: [20] Mochizuki, Y.; Koikegami, S.; Nakano, T.; Amari, S.; Kitaura, K. Large scale MP2 calculations with fragment molecular orbital scheme. Chem. Phys. Lett. 2004, 396, 473-479. – reference: [21] Mochizuki, Y.; Yamashita, K.; Nakano, T.; Okiyama, Y.; Fukuzawa, K.; et al. Higher-order correlated calculations based on fragment molecular orbital scheme. Theor. Chem. Acc. 2011, 130, 515-530. – reference: [22] Fukuzawa, K.; Nakano, T.; Kato, A.; Mochizuki, Y.; Tanaka, S. Applications of the fragment molecular orbital method for bio-macromolecules. J. Comp. Chem. Jpn. 2007, 6, 185-198. – reference: [10] Cornell, W. D.; Cieplak, P.; Bayly, C. I.; et al. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197. – reference: [19] Mochizuki, Y.; Nakano, T.; Koikegami, S.; Tanimori, S.; Abe, Y.; et al. A parallelized integral-direct second-order Møller-Plesset perturbation theory method with a fragment molecular orbital scheme. Theor. Chem. Acc. 2004, 112, 442-452. – reference: [9] Frisch M. J.; et al. Gaussian09. Revision A.02, Gaussian, Inc., Wallingford, CT, 2009. – reference: [11] Matsuo, M.; Hasegawa, A.; Takano, M.; Saito, H.; Kakuda, S.; et al. Synthesis of 2α-Heteroarylalkyl active vitamin D3 with therapeutic effect on enhancing bone mineral density in vivo. ACS Med. Chem. Lett. 2013, 4, 671-674. – reference: [12] Rochel, N.; Wurtz, J. M.; Mitschler, A.; Klaholz, B.; Moras, D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 2000, 5, 173-179. – reference: [3] Kàllay, E.; Bareis, P.; Bajna, E.; Kriwanek, S.; Bonner, E.; et al. Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress. Food Chem. Toxicol. 2002, 40, 1191-1196. – reference: [15] Case, D. A.; et al. AMBER 12. University of California, San Francisco, 2012. – reference: [4] Deeb, K. K.; Trump, D. L.; Johnson, C. S. Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat. Rev. Cancer 2007, 7, 684-700. |
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| Snippet | ビタミンD受容体（VDR）とキラリティーが異なる2種類のリガンド間の結合親和性が実験により解析され、リガンドのキラリティーの違いにより、VDRへの結合親和性が大きく変化することが見出された。この原因を明らかにするため、VDRと2種類のリガンド間の特異的相互作用を、ab initio... |
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| SubjectTerms | キラリティー ビタミンD受容体 フラグメント分子軌道 分子シミュレーション 特異的相互作用 結合親和性 |
| Title | ビタミンD受容体とキラリティが異なるリガンド間の特異的相互作用: ab initioフラグメント分子軌道計算 |
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