Prediction of the binding modes between macrolactin N and peptide deformylase from Staphylococcus aureus by molecular docking and molecular dynamics simulations

详细信息    查看全文

• 作者：Jian Gao (1)
  Yuanhua Cheng (1) (2)
  Wei Cui (1)
  Fushi Zhang (2)
  Huai Zhang (1)
  Yuguo Du (1)
  Mingjuan Ji (1)
  
• 关键词：Macrolactin N ; Peptide deformylase ; Docking ; Molecular dynamics simulation
• 刊名：Medicinal Chemistry Research
• 出版年：2013
• 出版时间：June 2013
• 年：2013
• 卷：22
• 期：6
• 页码：2889-2901
• 全文大小：923KB
• 参考文献：1. Apfel CM, Locher H, Evers S, Takacs B, Hubschwerlen C, Pirson W, Page MGP, Keck W (2001) Peptide deformylase as an antibacterial drug target: target validation and resistance development. Antimicrob Agents Chemother 45:1058-064 CrossRef
  2. Bayly CI, Cieplak P, Cornell W, Kollman PA (1993) A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J Phys Chem 97:10269-0280 CrossRef
  3. Boularot A, Giglione C, Petit S, Duroc Y, Alves de Sousa R, Larue V, Cresteil T, Dardel F, Artaud I, Meinnel T (2006) Discovery and refinement of a new structural class of potent peptide deformylase inhibitors. J Med Chem 50:10-0 CrossRef
  4. Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668-688 CrossRef
  5. Chen DZ, Patel DV, Hackbarth CJ, Wang W, Dreyer G, Young DC, Margolis PS, Wu C, Ni ZJ, Trias J, White RJ, Yuan Z (2000) Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry 39:1256-262 CrossRef
  6. Chen D, Hackbarth C, Ni ZJ, Wu C, Wang W, Jain R, He Y, Bracken K, Weidmann B, Patel DV, Trias J, White RJ, Yuan Z (2004) Peptide deformylase inhibitors as antibacterial agents: identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach. Antimicrob Agents Chemother 48:250-61 CrossRef
  7. Clark M, Richard D, Cramer I, Opdenbosch NV (1989) Validation of the general purpose tripos 5.2 force field. J Comput Chem 10:982-012 CrossRef
  8. Davies SJ, Ayscough AP, Beckett RP, Bragg RA, Clements JM, Doel S, Grew C, Launchbury SB, Perkins GM, Pratt LM, Smith HK, Spavold ZM, Thomas SW, Todd RS, Whittaker M (2003) Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1-side chain. Bioorg Med Chem Lett 13:2709-713 CrossRef
  9. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24:1999-012 CrossRef
  10. Essmann U, Perera L, Berkowitz M, Darden T, Lee H, Pedersen L (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577-593 CrossRef
  11. Falconer SB, Brown ED (2009) New screens and targets in antibacterial drug discovery. Curr Opin Microbiol 12:497-04 CrossRef
  12. Frisch MJ, Trucks GW, Schlegel HB et al (2004) Gaussian03, Revision C.02. Gaussian, Inc, Wallingford
  13. Gohlke H, Case DA (2004) Converging free energy estimates: MM–PB(GB)SA studies on the protein–protein complex Ras–Raf. J Comput Chem 25:238-50 CrossRef
  14. Gohlke H, Kiel C, Case DA (2003) Insights into protein–protein binding by binding free energy calculation and free energy decomposition for the Ras–Raf and Ras–Ral GDS complexes. J Mol Biol 330:891-13 CrossRef
  15. Groche D, Becker A, Schlichting I, Kabsch W, Schultz S, Wagner AFV (1998) Isolation and crystallization of functionally competent / Escherichia coli peptide deformylase forms containing either iron or nickel in the active site. Biochem Biophys Res Commun 246:342-46 CrossRef
  16. Guay DRP (2007) Drug forecast—the peptide deformylase inhibitors as antibacterial agents. Ther Clin Risk Manag 3:513-25
  17. Hamdache A, Lamarti A, Aleu J, Collado IG (2011) Non-peptide metabolites from the genus Bacillus. J Nat Prod 74:893-99 CrossRef
  18. Hou T, McLaughlin W, Lu B, Chen K, Wang W (2005) Prediction of binding affinities between the human amphiphysin-1 SH3 domain and its peptide ligands using homology modeling, molecular dynamics and molecular field analysis. J Proteome Res 5:32-3 CrossRef
  19. Hou T, Zhang W, Case DA, Wang W (2008) Characterization of domain–peptide interaction interface: a case study on the amphiphysin-1 SH3 domain. J Mol Biol 376:1201-214 CrossRef
  20. Howard MH, Cenizal T, Gutteridge S, Hanna WS, Tao Y, Totrov M, Wittenbach VA, Zheng YJ (2004) A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening. J Med Chem 47:6669-672 CrossRef
  21. Hu X, Nguyen KT, Verlinde CLMJ, Hol WGJ, Pei D (2003) Structure-based design of a macrocyclic inhibitor for peptide deformylase. J Med Chem 46:3771-774 CrossRef
  22. Hu X, Nguyen KT, Jiang VC, Lofland D, Moser HE, Pei D (2004) Macrocyclic inhibitors for peptide deformylase: a structure–activity relationship study of the ring size. J Med Chem 47:4941-949 CrossRef
  23. Jain R, Sundram A, Lopez S, Neckermann G, Wu C, Hackbarth C, Chen D, Wang W, Ryder NS, Weidmann B, Patel D, Trias J, White R, Yuan Z (2003) Alpha-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents. Bioorg Med Chem Lett 13:4223-228 CrossRef
  24. Jorgensen W, Chandrasekhar J, Madura J, Impey R, Klein M (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926-35 CrossRef
  25. Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889-97 CrossRef
  26. Kwon YJ, Sohn MJ, Zheng CJ, Kim WG (2007) Fumimycin: a peptide deformylase inhibitor with an unusual skeleton produced by / Aspergillus fumisynnematus. Org Lett 9:2449-451 CrossRef
  27. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283-91 CrossRef
  28. Leeds JA, Dean CR (2006) Peptide deformylase as an antibacterial target: a critical assessment. Curr Opin Pharmacol 6:445-52 CrossRef
  29. Leopoldini M, Russo N, Toscano M (2007) Which one among Zn(II), Co(II), Mn(II), and Fe(II) is the most efficient ion for the methionine aminopeptidase catalyzed reaction? J Am Chem Soc 129:7776-784 CrossRef
  30. Lofland D, Difuntorum S, Waller A, Clements JM, Weaver MK, Karlowsky JA, Johnson K (2004) In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698. J Antimicrob Chemother 53:664-68 CrossRef
  31. Lucchini G, Bianchetti R (1980) Initiation of protein synthesis in isolated mitochondria and chloroplasts. Biochim Biophys Acta 608:54-1 CrossRef
  32. Nguyen KT, Wu JC, Boylan JA, Gherardini FC, Pei D (2007) Zinc is the metal cofactor of / Borrelia burgdorferi peptide deformylase. Arch Biochem Biophys 468:217-25 CrossRef
  33. Onufriev A, Bashford D, Case DA (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins Struct Funct Bioinf 55:383-94 CrossRef
  34. Rajagopalan PTR, Yu XC, Pei D (1997) Peptide deformylase: a new type of mononuclear iron protein. J Am Chem Soc 119:12418-2419 CrossRef
  35. Rarey M, Kramer B, Lengauer T, Klebe G (1996) A fast flexible docking method using an incremental construction algorithm. J Mol Biol 261:470-89 CrossRef
  36. Ryckaert J, Ciccotti G, Berendsen H (1977) Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23:327-41 CrossRef
  37. Shen G, Zhu J, Simpson AM, Pei D (2008) Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors. Bioorg Med Chem Lett 18:3060-063 CrossRef
  38. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25:1157-174 CrossRef
  39. Wang J, Hou T, Xu X (2006) Recent advances in free energy calculations with a combination of molecular mechanics and continuum models. Curr Comput Aid Drug 2:287-06 CrossRef
  40. Watters AA, Jones RN, Leeds JA, Denys G, Sader HS, Fritsche TR (2006) Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-004). J Antimicrob Chemother 57:914-23 CrossRef
  41. Weiser J, Shenkin P, Still C (1999) Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO). J Comput Chem 20:217-30 CrossRef
  42. Xue CB, He X, Roderick J, DeGrado WF, Cherney RJ, Hardman KD, Nelson DJ, Copeland RA, Jaffee BD, Decicco CP (1998) Design and synthesis of cyclic inhibitors of matrix metalloproteinases and TNF-alpha production. J Med Chem 41:1745-748 CrossRef
  43. Yoo JS, Zheng CJ, Lee S, Kwak JH, Kim WG (2006) Macrolactin N, a new peptide deformylase inhibitor produced by / Bacillus subtilis. Bioorg Med Chem Lett 16:4889-892 CrossRef
  44. Yoon HJ, Kim HL, Lee SK, Kim HW, Kim HW, Lee JY, Mikami B, Suh SW (2004) Crystal structure of peptide deformylase from / Staphylococcus aureus in complex with actinonin, a naturally occurring antibacterial agent. Proteins Struct Funct Bioinf 57:639-42 CrossRef
  45. Yuan Z, White RJ (2006) The evolution of peptide deformylase as a target: contribution of biochemistry, genetics and genomics. Biochem Pharmacol 71:1042-047 CrossRef
  46. Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J (2009) Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Eur J Med Chem 44:2202-210 CrossRef
  47. Zheng CJ, Lee S, Lee CH, Kim WG (2007) Macrolactins O-R, glycosylated 24-membered lactones from Bacillus sp. AH159-1. J Nat Prod 70:1632-635 CrossRef
  48. Zhou Z, Song X, Gong W (2005) Novel conformational states of peptide deformylase from pathogenic bacterium / Leptospira interrogans: implications for population shift. J Biol Chem 280:42391-2396 CrossRef
  
• 作者单位：Jian Gao (1)
  Yuanhua Cheng (1) (2)
  Wei Cui (1)
  Fushi Zhang (2)
  Huai Zhang (1)
  Yuguo Du (1)
  Mingjuan Ji (1)
  
  1. College of Chemistry and Chemical Engineering, Graduate University of the Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China
  2. Key Laboratory of Organic Optoelectronics and Molecular Engineering of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China
  

文摘

Macrolactin N is a novel lactone compound against Staphylococcus aureus peptide deformylase (PDF) with an IC50 value of 7.5?μM, while its binding mode with PDF still remains largely unknown. In this study, the binding mechanism of macrolactin N to PDF was investigated using molecular docking, molecular dynamics (MD) simulations, and free energy calculations. Four typical binding modes were obtained by FlexX docking and cluster analysis, which are named as Model A, Model B, Model C, and Model D. The predicted binding free energy of Model A is more stable than those of the other three models. Besides, the free energy decomposition and structure analysis, as well as the hydrogen bond occupancy analysis further demonstrate that Model A is the most appropriate conformation for ligand binding. We found that the Zn2+ ion in Model A has positive contribution with the ligand, which implies the introduction of a metal chelating functional group on this model could further improve the binding affinity to PDF. The feasibility of the results of our molecular docking and MD simulation work was examined by the result about PDF-actinonin in terms of the theoretical simulation and the experimental results (e.g., crystal structure). Meanwhile, four predicted binding modes are validated by means of comparing their binding modes with actinonin, and the comparison result shows that the macrolactin N in Model A may have the highest similarity to the binding mode of actinonin. This work might be useful in designing more promising PDF inhibitors.