Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H+,K+-ATPase at different pH

详细信息    查看全文

• 作者：Hua-Jun Luo ; Jun-Zhi Wang ; Nian-Yu Huang…
• 关键词：H+ ; K+ ; ATPase ; Potassium ; competitive acid blockers ; Induced ; fit docking ; Binding free energy ; Protonated form
• 刊名：Journal of Computer-Aided Molecular Design
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：30
• 期：1
• 页码：27-37
• 全文大小：5,655 KB
• 参考文献：1.Li H, Meng L, Liu F, Wei JF, Wang YQ (2013) H+/K+-ATPase inhibitors: a patent review. Expert Opin Ther Pat 23:99–111CrossRef
  2.Jain KS, Shah AK, Bariwal J, Shelke SM, Kale AP et al (2007) Recent advances in proton pump inhibitors and management of acid-peptic disorders. Bioorg Med Chem 15:1181–1205CrossRef
  3.Shin JM, Munson K, Vagin O, Sachs G (2009) The gastric HK-ATPase: structure, function, and inhibition. Pflug Arch Eur J Physiol 457:609–622CrossRef
  4.Lee J, Simpson G, Scholes P (1974) An ATPase from dog gastric mucosa: changes of outer pH in suspensions of membrane vesicles accompanying ATP hydrolysis. Biochem Biophys Res Commun 60:825–832CrossRef
  5.Wolosin JM (1985) Ion transport studies with H+/K+-ATPase-rich vesicles: implications for HCl secretion and parietal cell physiology. Am J Physiol 248:G595–G607
  6.Shin JM, Sachs G (2006) Gastric H, K-ATPase as a drug target. Dig Dis Sci 51:823–833CrossRef
  7.Andersson K, Carlsson E (2005) Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. Pharmacol Ther 108:294–307CrossRef
  8.Sachs G, Shin JM, Vagin O, Lambrecht N, Yakubov I et al (2007) The gastric H, K-ATPase as a drug target: past, present, and future. J Clin Gastroenterol 41:S226–S242CrossRef
  9.Sachs G, Shin JM, Howden CW (2006) The clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther 23:S2–S8CrossRef
  10.Lee JW, Chae JS, Kim CS, Kim JK, Lim DS et al (1998) Pyrimidine derivatives and processes for the preparation thereof. US005750531A
  11.Li W, Yang Y, Tian Y, Xu X, Chen Y et al (2011) Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension. Int J Pharm 408:157–162CrossRef
  12.Fang HB, Jin L, Huang NY, Wang JZ, Zou K et al (2013) Synthesis, structure and H+/K+-ATPase inhibitory activity of novel triazolyl substituted tetrahydrobenzofuran derivatives via one-pot three-component click reaction. Chin J Chem 31:831–838CrossRef
  13.Abe K, Tani K, Nishizawa T, Fujiyoshi Y (2009) Inter-subunit interaction of gastric H+,K+-ATPase prevents reverse reaction of the transport cycle. EMBO J 28:1637–1643CrossRef
  14.Abe K, Tani K, Fujiyoshi Y (2011) Conformational rearrangement of gastric H+,K+-ATPase induced by an acid suppressant. Nat Commun 2:155–160CrossRef
  15.Kim CG, Watts JA, Watts A (2005) Ligand docking in the gastric H+/K+-ATPase: homology modeling of reversible Inhibitor binding sites. J Med Chem 48:7145–7152CrossRef
  16.Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN et al (2000) The protein data bank. Nucleic Acids Res 28:235–242CrossRef
  17.Shinoda T, Ogawa H, Cornelius F, Toyoshima C (2009) Crystal structure of the sodium-potassium pump at 2.4 Å resolution. Nature 459:446–450CrossRef
  18.Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402CrossRef
  19.Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ et al (2003) Multiple sequence alignment with the clustal series of programs. Nucleic Acids Res 31:3497–3500CrossRef
  20.Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial sestraints. J Mol Biol 234:779–815CrossRef
  21.Schrödinger, LLC, New York (2010). www.​schrodinger.​com
  22.Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225–11236CrossRef
  23.Laskowski RA, MacArthur MW, Moss DS, Thomton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291CrossRef
  24.LigPrep, version 2.4, Schrödinger, LLC, New York, NY (2010)
  25.Shelley JC, Cholleti A, Frye L, Greenwood JR, Timlin MR et al (2007) Epik: a software program for pKa prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des 21:681–691CrossRef
  26.Sherman W, Day T, Jacobson MP, Friesner RA, Farid R (2006) Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 49:534–553CrossRef
  27.Zhong H, Tran LM, Stang JL (2009) Induced-fit docking studies of the active and inactive states of protein tyrosine kinases. J Mol Graph Model 28:336–346CrossRef
  28.Wanga H, Aslanian R, Madison VS (2008) Induced-fit docking of mometasone furoate and further evidence for glucocorticoid receptor 17α pocket flexibility. J Mol Graph Model 27:512–521CrossRef
  29.Luo HJ, Wang JZ, Deng WQ, Zou K (2013) Induced-fit docking and binding free energy calculation on furostanol saponins from Tupistra chinensis as epidermal growth factor receptor inhibitors. Med Chem Res 22:4970–4979CrossRef
  30.Glide, version 5.6, Schrödinger, LLC, New York, NY (2010)
  31.Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR et al (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49:6177–6196CrossRef
  32.Vagin O, Denevich S, Munson K, Sachs G (2002) SCH 28080, a K+-competitive inhibitor of the gastric H, K-ATPase, binds near the M5-6 luminal loop, preventing K+ access to the ion binding domain. Biochemistry 41:12755–12762CrossRef
  33.Munson K, Gutierrez C, Balaji VN, Ramnarayan K, Sachs G (1991) Identification of an extracytoplasmic region of H+,K+-ATPase labeled by a K+-competitive photoaffinity inhibitor. J Biol Chem 266:18976–18988
  34.Asano S, Matsuda S, Tega Y, Shimizu K, Sakamoto S et al (1997) Mutational analysis of putative SCH28080 binding sites of the gastric H+,K+-ATPase. J Biol Chem 272:17668–17674CrossRef
  35.Vagin O, Munson K, Lambrecht N, Karlish SJD, Sachs G (2000) Mutational analysis of the K+-competitive inhibitor site of gastric H, K-ATPase. Biochemistry 40:7480–7490CrossRef
  36.Munson K, Law RJ, Sachs G (2007) Analysis of the gastric H, K-ATPase for ion pathways and inhibitor binding sites. Biochemistry 46:5398–5417CrossRef
  37.Jacobson MP, Pincus DL, Rapp CS, Day TJF, Honig B et al (2004) A hierarchical approach to all-atom protein loop prediction. Proteins 55:351–367CrossRef
  38.Murphy RB, Philipp DM, Friesner RA (2000) A mixed quantum mechanics/molecular mechanics (QM/MM) method for large-scale modeling of chemistry in protein environments. J Comp Chem 21:1442–1457CrossRef
  39.Philipp DM, Friesner RA (1999) Mixed ab initio QM/MM modeling using frozen orbitals and tests with alanine dipeptide and tetrapeptide. J Comp Chem 20:1468–1494CrossRef
  40.Kollman PA, Massova I, Reyes C, Kuhn B, Huo S et al (2011) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889–897CrossRef
  41.Massova I, Kollman PA (2000) Combined molecular mechanical and continuum solvent approach (MM–PBSA/GBSA) to predict ligand binding. Perspect Drug Discov Des 18:113–135CrossRef
  42.MacroModel, version 9.8, Schrödinger, LLC, New York, NY (2010)
  43.Saccomani G, Stewart HB, Show D, Lewin M, Sachs G (1977) Characterization of gastric mucosal membranes. Biochem Biophys Acta 465:311–330CrossRef
  44.Yoon YA, Park CS, Cha MH, Choi H, Simm JY et al (2010) Novel pyrimidines as acid pump antagonists (APAs). Bioorg Med Chem Lett 20:5735–5738CrossRef
  45.ACD/I-Lab, version 12.01 (2013) Advanced Chemistry Development, Inc., Toronto. www.​acdlabs.​com
  46.Maestro, version 9.3, Schrödinger, LLC, New York, NY (2012)
  
• 作者单位：Hua-Jun Luo (1)
  Jun-Zhi Wang (1)
  Nian-Yu Huang (1)
  Wei-Qiao Deng (1) (2)
  Kun Zou (1)
  
  1. Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, China
  2. State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Physical Chemistry
  Computer Applications in Chemistry
  Animal Anatomy, Morphology and Histology
  
• 出版者：Springer Netherlands
• ISSN：1573-4951

文摘

The interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives (compound 1 (N, N-Dipropyl-1-(2-phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-1H-1,2,3-triazole-4-methanamine) and 2 (1-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-4-(morpholin-4-ylmethyl)-1H-1,2,3-triazole)) with H+,K+-ATPase at different pH were studied by induced-fit docking, QM/MM optimization and MM/GBSA binding free energy calculations of two forms (neutral and protonated form) of compounds. The inhibition activity of compound 1 is measured and almost unchanged at different pH, while the activity of compound 2 increases significantly with pH value decreased. This phenomenon could be explained by their protonated form percentages and the calculated binding free energies of protonated and neutral mixture of compounds at different pH. The binding free energy of protonated form is higher than that of neutral form of compound, and the protonated form could be a powerful inhibitor of H+,K+-ATPase. By the decomposed energy comparisons of residues in binding sites, Asp137 should be the key binding site to protonated form of compound because of the hydrogen bond and electrostatic interactions. These calculation results could help for further rational design of novel H+,K+-ATPase inhibitors. Keywords H+,K+-ATPase Potassium-competitive acid blockers Induced-fit docking Binding free energy Protonated form