Theoretical Analysis of Activity Cliffs among Benzofuranone-Class Pim1 Inhibitors Using the Fragment Molecular Orbital Method with Molecular Mechanics Poisson-Boltzmann Surface Area (FMO+MM-PBSA) Approach
作者： Chiduru Watanabe , Hirofumi Watanabe , Kaori Fukuzawa , Lorien J. Parker , Yoshio Okiyama
关键词:
摘要: Significant activity changes due to small structural (i.e., cliffs) of serine/threonine kinase Pim1 inhibitors were studied theoretically using the fragment molecular orbital method with mechanics Poisson–Boltzmann surface area (FMO+MM-PBSA) approach. This methodology enables quantum-chemical calculations for large biomolecules solvation. In course drug discovery targeting Pim1, six benzofuranone-class found differ only in position indole-ring nitrogen atom. By comparing various qualities complex structures based on X-ray, classical (MM)-optimized, and quantum/molecular (QM/MM)-optimized structures, we that QM/MM-optimized provided best correlation (R2 = 0.85) between pIC50 calculated FMO+MM-PBSA binding energy. Combining solvation energy QM was important increase correlation. addition, decomposition interaction en...
rcsb.org
acs.org
elsevier.com参考文章(72)
Dagmar Stumpfe, Jürgen Bajorath, Exploring Activity Cliffs in Medicinal Chemistry Journal of Medicinal Chemistry. ,vol. 55, pp. 2932- 2942 ,(2012) , 10.1021/JM201706B
Jaime Pérez-Villanueva, Oscar Méndez-Lucio, Olivia Soria-Arteche, José L. Medina-Franco, Activity cliffs and activity cliff generators based on chemotype-related activity landscapes. Molecular Diversity. ,vol. 19, pp. 1021- 1035 ,(2015) , 10.1007/S11030-015-9609-Z
Hirofumi Watanabe, Shigenori Tanaka, Noriaki Okimoto, Aki Hasegawa, Makoto Taiji, Yoshiaki Tanida, Takashi Mitsui, Mariko Katsuyama, Hideaki Fujitani, Comparison of binding affinity evaluations for FKBP ligands with state-of-the-art computational methods: FMO, QM/MM, MM-PB/SA and MP-CAFEE approaches Chem-bio Informatics Journal. ,vol. 10, pp. 32- 45 ,(2010) , 10.1273/CBIJ.10.32
Stella Manta, Andromachi Xipnitou, Christos Kiritsis, Anastassia L. Kantsadi, Joseph M. Hayes, Vicky T. Skamnaki, Christos Lamprakis, Maria Kontou, Panagiotis Zoumpoulakis, Spyridon E. Zographos, Demetres D. Leonidas, Dimitri Komiotis, 3′-Axial CH2OH Substitution on Glucopyranose does not Increase Glycogen Phosphorylase Inhibitory Potency. QM/MM-PBSA Calculations Suggest Why Chemical Biology & Drug Design. ,vol. 79, pp. 663- 673 ,(2012) , 10.1111/J.1747-0285.2012.01349.X
Tatsusada Yoshida, Kenji Yamagishi, Hiroshi Chuman, QSAR Study of Cyclic Urea Type HIV‐1 PR Inhibitors Using Ab Initio MO Calculation of Their Complex Structures with HIV‐1 PR Qsar & Combinatorial Science. ,vol. 27, pp. 694- 703 ,(2008) , 10.1002/QSAR.200730108
Motohiro Nishio, The CH/π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates Physical Chemistry Chemical Physics. ,vol. 13, pp. 13873- 13900 ,(2011) , 10.1039/C1CP20404A
R. Amson, F. Sigaux, S. Przedborski, G. Flandrin, D. Givol, A. Telerman, The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias Proceedings of the National Academy of Sciences of the United States of America. ,vol. 86, pp. 8857- 8861 ,(1989) , 10.1073/PNAS.86.22.8857
Isao Nakanishi, Dmitri G. Fedorov, Kazuo Kitaura, Molecular recognition mechanism of FK506 binding protein: An all-electron fragment molecular orbital study Proteins: Structure, Function, and Bioinformatics. ,vol. 68, pp. 145- 158 ,(2007) , 10.1002/PROT.21389
Jayashree Srinivasan, Thomas E. Cheatham, Piotr Cieplak, Peter A. Kollman, David A. Case, Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices Journal of the American Chemical Society. ,vol. 120, pp. 9401- 9409 ,(1998) , 10.1021/JA981844+