王乾韜

王乾韜，男，博士，四川大學華西藥學院特聘副研究員。

基本介紹

• 中文名：王乾韜
• 國籍：中國
• 畢業院校：英國曼徹斯特大學
• 學位/學歷：博士
• 職稱：副研究員

人物經歷

2005-2009 英國曼徹斯特大學藥學院，博士（導師：Richard Bryce）

2002-2005 英國曼徹斯特大學物理與天文學院，學士

2017-至今 四川大學華西藥學院，副教授 (兼任學院學科發展建設辦公室主任)

2015-2017 四川大學 華西藥學院，特聘副研究員

2012-2015 美國得州大學奧斯丁 藥學院，博士後（導師： Kevin Dalby & Pengyu Ren）

2010-2012 美國羅格斯-新澤西州立大學BioMaps Institute，博士後（導師： David Case）

研究方向

（1）計算機輔助藥物設計、分子動力學模擬：

利用GPU加速的戒己廈自建高性能計算機集群對藥物與受體、離子通道、激酶等大茅乘鴉想分子轎危蛋白的結合過程、能量、結構等進行分子動力學模擬，實現對蛋白質結構在原子層面的動態觀察與研究，並套用於藥物設計中。

藥物研發具有周期長、花費大的特點，因此目前的一個前沿研究方向即是通過計算機人工智慧為輔助手段，解決藥物設計中的痛點和難點問題。如：課題組與美國得州大學藥學院Kevin Dalby教授合作，成功從300萬個小分子中篩選得到了多個具有潛在抗腫瘤活性的小分子化合物，並在鍵捆紙後期實驗中驗證；與四川大學華西藥學院同事利用多學科交叉，成功探明了一類中藥提取物的生物學靶點，並闡明了其增強學習記憶能力的藥理作用機制等。

（2）抗神經退行性、抗腫瘤藥物的發現與開發：

神經退行性疾病與腫瘤是影響國民健康的兩大頑疾，具有極其巨大的臨床需求及重要的社會經濟意義。課題組通櫻匙肯過計算化學、合成化學、化學生物學等手段致力於基於靶點的藥物發現與設計（eEF2K, PERK, MELK, GABAAR, SK3等）、以及基於天然來源的藥物分子的靶點尋找、機理研究及衍生物的設甩洪幾燥計與開發。

（3）理論方法及軟體開發（AMBER, AMOEBA and etc.）

計算精度與計算速度的矛盾是目前現有分子模擬技術有一個極大的挑戰。或者簡單來講，即：計算速度與計算準確度不可兼得的問題。課題組長期與美國分子模擬領域大師David Case及Pengyu Ren教授合作和翻院，參與了國際知名分子動力學模擬力場Amber與 AMOEBA的開發工作，並致力於新一代前沿可極化電荷轉移分子力場模型的開發工作。

軟體開發

（1）ParmOpt參數擬合軟體（獨立開發，Wang，Q.T. et al., 2015, J. Chem. Theory Comput., pp. 2609-2618）

（2）世界知名分子動力學模擬軟體包Amber（參與開發）

（3）世界知名可極化分子力場模型AMOEBA力場（參與開發）

科研項目

2017-2019 國家自然科學基金青年基金

2015-2018 四川大學引進人才科研啟動經費資助項目

發表論文

1.Liu, F.-R.; Jin, H.; Wang, Y.; Chen, C.; Li, M.; Mao, S.-J.; Wang, Q.T.*; Li, H.*, “Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia”, Drug Delivery, 2017, 24, 882-890

2.Deng, S.; Wang, Q.T.*; and Ren, P.Y.*, “Estimating and modeling charge transfer from the SAPT induction energy”, Journal of Computational Chemistry, 2017, 38, 2222-2231

3.Rockers, JA ; Wang, QT; Liu, CW; Piquemal, JP; Ren, PY; Ponder, JW, “An optimized charge penetration model for use with the AMOEBA force field”, Physical Chemistry and Chemical Physics, 2017, 19, 276-291

4.Edupuganti, R; Taliaferro, JM; Wang, QT; Xie, X; Cho, EJ; Vidhu, F; Ren, P; Anslyn, EV; Bartholomeusz, C; Dalby, KN, “Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth”, Bioorganic & Medicinal Chemistry, 2017, 25, 2609-2616

5.Liu, CW; Qi, R; Wang, QT; Piquemal, JP; Ren, PY, “Capturing Many-Body Interactions with Classical Dipole Induction Models”, Journal of Chemical Theory and Computation, 2017, 13, 2751-2761

6.Wang, Y; Liu, FR; Wang, QT; Xiang, HL; Jin, H; Li, H; Mao, SJ, “A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells”, International Journal of Pharmaceutics, 2017, 529, 531-542

7.Qi, R. ;† Wang, Q.T.;† and Ren, P.Y., “General van der Waals potential for common organic molecules”, Bioorgan. Med. Chem., 2016, 24, 4911-4919 (†共同一作)

8.Narth, C.; Lagardere, L.; Polack, E.; Gresh, N.; Wang, Q.T.; Bell, D.R.; Rackers, J.A.; Ponder, J.W.; Ren, P.Y.; Piquemal, J.-P., “Scalable improvement of SPME multipolar electrostatics in anisotropic polarizable molecular mechanics using a general short-range penetration correction up to quadrupoles”, J. Comp. Chem., 2016 ,37 (5), 494-506

9.Wang, Q.T.; Rackers, J.A.; He, C.; Qi, R.; Narth, C.; Lagardere, L.; Gresh, N.; Ponder, J.W.; Piquemal, J.-P.; Ren, P.Y., “General model for treating short-range electrostatic penetration in a molecular mechanics force field”, Journal of Chemical Theory and Computation, 2015, 11, 2609-2618

10.Wang, Q.T.; Edupuganti, R.; Tavares, C.D.J.; Dalby, K.N. and Ren, P., “Using docking and alchemical free energy perturbation to determine the binding mechanism of eEF2K inhibitors and prioritizing the compound synthesis”, Frontiers in Molecular Biosciences, section Molecular Recognition, 2015, 2, 9

11.Qi, R.; Wang, L.-P.; Wang, Q.T.; Pande, V.; Ren, P.Y., “United polarizable multipole water model for molecular mechanics simulation”, J. Chem. Phys., 2015, 143, 014504

12.Zhang, C.; Lu, C.; Wang, Q.T.; Ponder, J.W.; Ren, P., “Polarizable Multipole-Based Force Field for Dimethyl and Trimethyl Phosphate”, Journal of Chemical Theory and Computation, 2015, 11, 5326-39

13.Li, J.; Zheng, Y.; Yu, X.L.; Lv, S.Y.; Wang, Q.T.; Hai, L.; Wu, Y., “Synthesis of isatins by the palladium-catalyzed intramolecular acylation of unactivated aryl C(sp(2))-H bonds”, RCS Advances, 2015, 5 (125), 103280-103283

14.Wang, Q.T.; Park, J.H.; Devokota, A.; Cho, E.J.; Dalby, K.N. and Ren, P., “Identification and validation of novel PERK inhibitors”, J. Chem. Inf. Model., 2014, 54, 1467–1475

15.Mu, X.;† Wang, Q.T.;† Wang, L.P.; Fried, S.D.; Piquemal, J.P.; Dalby, K.N.; and Ren, P., “Modeling Organochlorine Compounds and the σ-hole Effect Using a Polarizable Multipole Force Field”, J. Phys. Chem. B, 2014, 118 (24), pp 6456–6465, （†共同一作 ）

16.Edupugantia, R.;† Wang, Q.T.;† Tavaresc, C.D.J.;† Chitjian, C.A.; Bachmanb, J.L.; Ren, P.; Anslynb, E.V. and Dalbya, K.N., “Synthesis and Biological Evaluation of Pyrido[2,3-d]pyrimidine-2,4-dione Derivatives as eEF-2K Inhibitors”, Bioorganic & Medicinal Chemistry, 2014, 22, 4910-4916, （†共同一作）

17.Abella, J.R.; Cheng,S.Y.; Wang, Q.T.; Yang, W. and Ren, P., “Hydration Free Energy from Orthogonal Space Random Walk and Polarizable Force Field”, J. Chem. Theory Comput., 2014, 10, 2792-2801

18.Devkota, A.K.; Edupugantia, R.; Yan, C.; Shi, Y.; Jose, J.; Wang, Q.T.; Kaoud, T.S.; Cho, E.J.; Ren, P. and Dalby, K.N., “Reversible Covalent Inhibition of eEF-2K by Carbonitriles”, ChemBioChem, 2014, 15, 2435-2442

19.Tavares, C.D.J.; Ferguson, S.B.; Giles, D.H.; Wang, Q.T.; Wellmann, R.M.; Warthaka, M/; Ren, P. and Dalby, K.N., “The Molecular Mechanism of Eukaryotic Elongation Factor 2 Kinase Activation”, J. Bio. Chem. 2014, 289, 23901-23916

20.Wang, Q.T. and Bryce, R.A. “Accounting for non-optimal interactions in molecular recognition: a study of ion-pi complexes using a QM/MM model with a dipole-polarisable MM region”, Phys. Chem. Chem. Phys., 2011, 13, 19401-19408

21.Wang, Q.T. and Bryce, R.A. “Improved hydrogen bonding at the NDDO-based semi-empirical quantum mechanical/molecular mechanical interface”, Journal of Chemical Theory and Computation, 2009, 5, 2206-2211

22.Ramraj, A.; Raju, R.K.; Wang, Q.T.; Hillier, I.H.; Bryce, R.A.; Vincent, M.A. “An evaluation of the GLYCAM06 and MM3 force field, and the PM3-D molecular orbital method for modeling prototype carbohydrate-aromatic interactions”, J. Mol. Graph. Model., 2010, 29, 321-325

23.Fong P.; Meng L.; Wang Q.T.; Chan M., “Inspiration of the England Community Pharmacy Services for the Development of Pharmacy in China”, China Pharmacy, 2011, 22, 4215-4218

24.Xia, Z.; Wang, Q.T.; Mu, X. and Ren, P., “Development of AMOEBA force field with advanced electrostatics, 2014, p83, Book Chapter, Ed. Zhou, R. CRC Press

國際會議

1.“Charge Penetration in Molecular Mechanics”, TSRC Molecular Recognition Workshop, 2015, Telluride, Colorado

2.“Modeling Intermolecular Forces in Molecular Recognition”, TSRC Molecular Recognition Workshop, 2014, Telluride, Colorado

3.“Discovery of Novel PERK Inhibitors using Machine Learning”, New Frontiers in Therapeutic Agents: Successes in Drugging the Undruggable, 2014, Houston, Texas

4.“Virtual screening of PERK inhibitors”, ACS 246th National Meeting, 2013, Indianapolis, Indiana

5.“Study of the non-covalent interaction energy functions in force field models against the decomposed quantum mechanical result”, ACS 246th National Meeting, 2013, Indianapolis, Indiana

6.“Modeling protein-ligand interactions using QM/MM methods” on Theory and Applications of Computational Chemistry (TACC) 2008 international conference in Shanghai

1.Liu, F.-R.; Jin, H.; Wang, Y.; Chen, C.; Li, M.; Mao, S.-J.; Wang, Q.T.*; Li, H.*, “Anti-CD123 antibody-modified niosomes for targeted delivery of daunorubicin against acute myeloid leukemia”, Drug Delivery, 2017, 24, 882-890

2.Deng, S.; Wang, Q.T.*; and Ren, P.Y.*, “Estimating and modeling charge transfer from the SAPT induction energy”, Journal of Computational Chemistry, 2017, 38, 2222-2231

3.Rockers, JA ; Wang, QT; Liu, CW; Piquemal, JP; Ren, PY; Ponder, JW, “An optimized charge penetration model for use with the AMOEBA force field”, Physical Chemistry and Chemical Physics, 2017, 19, 276-291

4.Edupuganti, R; Taliaferro, JM; Wang, QT; Xie, X; Cho, EJ; Vidhu, F; Ren, P; Anslyn, EV; Bartholomeusz, C; Dalby, KN, “Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth”, Bioorganic & Medicinal Chemistry, 2017, 25, 2609-2616

5.Liu, CW; Qi, R; Wang, QT; Piquemal, JP; Ren, PY, “Capturing Many-Body Interactions with Classical Dipole Induction Models”, Journal of Chemical Theory and Computation, 2017, 13, 2751-2761

6.Wang, Y; Liu, FR; Wang, QT; Xiang, HL; Jin, H; Li, H; Mao, SJ, “A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells”, International Journal of Pharmaceutics, 2017, 529, 531-542

7.Qi, R. ;† Wang, Q.T.;† and Ren, P.Y., “General van der Waals potential for common organic molecules”, Bioorgan. Med. Chem., 2016, 24, 4911-4919 (†共同一作)

8.Narth, C.; Lagardere, L.; Polack, E.; Gresh, N.; Wang, Q.T.; Bell, D.R.; Rackers, J.A.; Ponder, J.W.; Ren, P.Y.; Piquemal, J.-P., “Scalable improvement of SPME multipolar electrostatics in anisotropic polarizable molecular mechanics using a general short-range penetration correction up to quadrupoles”, J. Comp. Chem., 2016 ,37 (5), 494-506

9.Wang, Q.T.; Rackers, J.A.; He, C.; Qi, R.; Narth, C.; Lagardere, L.; Gresh, N.; Ponder, J.W.; Piquemal, J.-P.; Ren, P.Y., “General model for treating short-range electrostatic penetration in a molecular mechanics force field”, Journal of Chemical Theory and Computation, 2015, 11, 2609-2618

10.Wang, Q.T.; Edupuganti, R.; Tavares, C.D.J.; Dalby, K.N. and Ren, P., “Using docking and alchemical free energy perturbation to determine the binding mechanism of eEF2K inhibitors and prioritizing the compound synthesis”, Frontiers in Molecular Biosciences, section Molecular Recognition, 2015, 2, 9

11.Qi, R.; Wang, L.-P.; Wang, Q.T.; Pande, V.; Ren, P.Y., “United polarizable multipole water model for molecular mechanics simulation”, J. Chem. Phys., 2015, 143, 014504

12.Zhang, C.; Lu, C.; Wang, Q.T.; Ponder, J.W.; Ren, P., “Polarizable Multipole-Based Force Field for Dimethyl and Trimethyl Phosphate”, Journal of Chemical Theory and Computation, 2015, 11, 5326-39

13.Li, J.; Zheng, Y.; Yu, X.L.; Lv, S.Y.; Wang, Q.T.; Hai, L.; Wu, Y., “Synthesis of isatins by the palladium-catalyzed intramolecular acylation of unactivated aryl C(sp(2))-H bonds”, RCS Advances, 2015, 5 (125), 103280-103283

14.Wang, Q.T.; Park, J.H.; Devokota, A.; Cho, E.J.; Dalby, K.N. and Ren, P., “Identification and validation of novel PERK inhibitors”, J. Chem. Inf. Model., 2014, 54, 1467–1475

15.Mu, X.;† Wang, Q.T.;† Wang, L.P.; Fried, S.D.; Piquemal, J.P.; Dalby, K.N.; and Ren, P., “Modeling Organochlorine Compounds and the σ-hole Effect Using a Polarizable Multipole Force Field”, J. Phys. Chem. B, 2014, 118 (24), pp 6456–6465, （†共同一作 ）

16.Edupugantia, R.;† Wang, Q.T.;† Tavaresc, C.D.J.;† Chitjian, C.A.; Bachmanb, J.L.; Ren, P.; Anslynb, E.V. and Dalbya, K.N., “Synthesis and Biological Evaluation of Pyrido[2,3-d]pyrimidine-2,4-dione Derivatives as eEF-2K Inhibitors”, Bioorganic & Medicinal Chemistry, 2014, 22, 4910-4916, （†共同一作）

17.Abella, J.R.; Cheng,S.Y.; Wang, Q.T.; Yang, W. and Ren, P., “Hydration Free Energy from Orthogonal Space Random Walk and Polarizable Force Field”, J. Chem. Theory Comput., 2014, 10, 2792-2801

18.Devkota, A.K.; Edupugantia, R.; Yan, C.; Shi, Y.; Jose, J.; Wang, Q.T.; Kaoud, T.S.; Cho, E.J.; Ren, P. and Dalby, K.N., “Reversible Covalent Inhibition of eEF-2K by Carbonitriles”, ChemBioChem, 2014, 15, 2435-2442

19.Tavares, C.D.J.; Ferguson, S.B.; Giles, D.H.; Wang, Q.T.; Wellmann, R.M.; Warthaka, M/; Ren, P. and Dalby, K.N., “The Molecular Mechanism of Eukaryotic Elongation Factor 2 Kinase Activation”, J. Bio. Chem. 2014, 289, 23901-23916

20.Wang, Q.T. and Bryce, R.A. “Accounting for non-optimal interactions in molecular recognition: a study of ion-pi complexes using a QM/MM model with a dipole-polarisable MM region”, Phys. Chem. Chem. Phys., 2011, 13, 19401-19408

21.Wang, Q.T. and Bryce, R.A. “Improved hydrogen bonding at the NDDO-based semi-empirical quantum mechanical/molecular mechanical interface”, Journal of Chemical Theory and Computation, 2009, 5, 2206-2211

22.Ramraj, A.; Raju, R.K.; Wang, Q.T.; Hillier, I.H.; Bryce, R.A.; Vincent, M.A. “An evaluation of the GLYCAM06 and MM3 force field, and the PM3-D molecular orbital method for modeling prototype carbohydrate-aromatic interactions”, J. Mol. Graph. Model., 2010, 29, 321-325

23.Fong P.; Meng L.; Wang Q.T.; Chan M., “Inspiration of the England Community Pharmacy Services for the Development of Pharmacy in China”, China Pharmacy, 2011, 22, 4215-4218

24.Xia, Z.; Wang, Q.T.; Mu, X. and Ren, P., “Development of AMOEBA force field with advanced electrostatics, 2014, p83, Book Chapter, Ed. Zhou, R. CRC Press

國際會議

1.“Charge Penetration in Molecular Mechanics”, TSRC Molecular Recognition Workshop, 2015, Telluride, Colorado

2.“Modeling Intermolecular Forces in Molecular Recognition”, TSRC Molecular Recognition Workshop, 2014, Telluride, Colorado

3.“Discovery of Novel PERK Inhibitors using Machine Learning”, New Frontiers in Therapeutic Agents: Successes in Drugging the Undruggable, 2014, Houston, Texas

4.“Virtual screening of PERK inhibitors”, ACS 246th National Meeting, 2013, Indianapolis, Indiana

5.“Study of the non-covalent interaction energy functions in force field models against the decomposed quantum mechanical result”, ACS 246th National Meeting, 2013, Indianapolis, Indiana

6.“Modeling protein-ligand interactions using QM/MM methods” on Theory and Applications of Computational Chemistry (TACC) 2008 international conference in Shanghai