Exploring transition pathway and free-energy profile of large-scale protein conformational change by combining normal mode analysis and umbrella sampling molecular dynamics

Journal of Physical Chemistry B

Volumn 118, Issue 1, 2014, Pages 134-143

  Wang, Jinan ^a   Shao, Qiang ^a   Xu, Zhijian ^a   Liu, Yingtao ^a   Yang, Zhuo ^a   Cossins, Benjamin P ^b   Jiang, Hualiang ^a   Chen, Kaixian ^a   Shi, Jiye ^b   Zhu, Weiliang ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b UCB PHARMA   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL SYSTEMS; CAMS; CONFORMATIONS; ENERGY BARRIERS; ENZYMES; FREE ENERGY; LIGANDS; MOLECULAR DYNAMICS;

CONFORMATIONAL CHANGE; CONFORMATIONAL INTERCONVERSION; CONFORMATIONAL TRANSITION PATHWAY; CONFORMATIONAL TRANSITIONS; FREE-ENERGY DIFFERENCE; INDUCED-FIT MECHANISM; MOLECULAR DYNAMICS SIMULATIONS; PROTEIN CONFORMATIONAL CHANGES;

CALMODULIN;

ADENYLATE KINASE; CALMODULIN; MITOGEN ACTIVATED PROTEIN KINASE P38;

ARTICLE; CHEMISTRY; METABOLISM; MOLECULAR DYNAMICS; PROTEIN CONFORMATION; THERMODYNAMICS;

ADENYLATE KINASE; CALMODULIN; MOLECULAR DYNAMICS SIMULATION; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN CONFORMATION; THERMODYNAMICS;

EID: 84892565867     PISSN: 15206106     EISSN: 15205207     Source Type: Journal    
DOI: 10.1021/jp4105129     Document Type: Article

References (81)

1. Bakan, A.; Bahar, I. The Intrinsic Dynamics of Enzymes Plays a Dominant Role in Determining the Structural Changes Induced upon Inhibitor Binding Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 14349-14354
2. Grant, B. J.; Gorfe, A. A.; McCammon, J. A. Large Conformational Changes in Proteins: Signaling and Other Functions Curr. Opin. Struct. Biol. 2010, 20, 142-147
3. Koshland, D. E. Application of a Theory of Enzyme Specificity to Protein Synthesis Proc. Natl. Acad. Sci. U.S.A. 1958, 44, 98-104
4. Tsai, C. J.; Ma, B. Y.; Nussinov, R. Folding and Binding Cascades: Shifts in Energy Landscapes Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9970-9972
5. Volkman, B. F.; Lipson, D.; Wemmer, D. E.; Kern, D. Two-State Allosteric Behavior in a Single Domain Signaling Protein Science 2001, 291, 2429-2433
6. Boehr, D. D.; Nussinov, R.; Wright, P. E. The Role of Dynamic Conformational Ensembles in Biomolecular Recognition Nat. Chem. Biol. 2009, 5, 789-796
7. Kokkinidis, M.; Glykos, N. M.; Fadouloglou, V. E. Protein Flexibility and Enzymatic Catalysis Adv. Protein Chem. Struct. Biol. 2012, 87, 181-218
8. Westenhoff, S.; Nazarenko, E.; Malmerberg, E.; Davidsson, J.; Katona, G.; Neutze, R. Time-Resolved Structural Studies of Protein Reaction Dynamics: A Smorgasbord of X-Ray Approaches Acta. Crystallogr., Sect. A 2010, 66, 207-219
9. Dror, R. O.; Dirks, R. M.; Grossman, J. P.; Xu, H. F.; Shaw, D. E. Biomolecular Simulation: A Computational Microscope for Molecular Biology Annu. Rev. Biophys. 2012, 41, 429-452
10. Skjaerven, L.; Reuter, N.; Martinez, A. Dynamics, Flexibility and Ligand-Induced Conformational Changes in Biological Macromolecules: A Computational Approach Future Med. Chem. 2011, 3, 2079-2100
11. Karplus, M.; McCammon, J. A. Molecular Dynamics Simulations of Biomolecules Nat. Struct. Biol. 2002, 9, 646-652
12. Hansson, T.; Oostenbrink, C.; van Gunsteren, W. Molecular Dynamics Simulations Curr. Opin. Struct. Biol. 2002, 12, 190-196
13. Klepeis, J. L.; Lindorff-Larsen, K.; Dror, R. O.; Shaw, D. E. Long-Timescale Molecular Dynamics Simulations of Protein Structure and Function Curr. Opin. Struct. Biol. 2009, 19, 120-127
14. Schlitter, J.; Engels, M.; Kruger, P. Targeted Molecular Dynamics: A New Approach for Searching Pathways of Conformational Transitions J. Mol. Graphics 1994, 12, 84-89
15. Hamelberg, D.; Mongan, J.; McCammon, J. A. Accelerated Molecular Dynamics: A Promising and Efficient Simulation Method for Biomolecules J. Chem. Phys. 2004, 120, 11919-11929
16. Bussi, G.; Laio, A.; Parrinello, M. Equilibrium Free Energies from Nonequilibrium Metadynamics Phys. Rev. Lett. 2006, 96, 090601
17. Hansmann, U. H. E. Parallel Tempering Algorithm for Conformational Studies of Biological Molecules Chem. Phys. Lett. 1997, 281, 140-150
18. Banavali, N. K.; Roux, B. Free Energy Landscape of A-DNA to B-DNA Conversion in Aqueous Solution J. Am. Chem. Soc. 2005, 127, 6866-6876
19. Berteotti, A.; Cavalli, A.; Branduardi, D.; Gervasio, F. L.; Recanatini, M.; Parrinello, M. Protein Conformational Transitions: The Closure Mechanism of a Kinase Explored by Atomistic Simulations J. Am. Chem. Soc. 2008, 131, 244-250
20. Fornili, A.; Giabbai, B.; Garau, G.; Degano, M. Energy Landscapes Associated with Macromolecular Conformational Changes from Endpoint Structures J. Am. Chem. Soc. 2010, 132, 17570-17577
21. Elber, R. Simulations of Allosteric Transitions Curr. Opin. Struct. Biol. 2011, 21, 167-172
22. Yu, H. B.; Ma, L.; Yang, Y.; Cui, Q. Mechanochemical Coupling in the Myosin Motor Domain. I. Insights from Equilibrium Active-Site Simulations PLoS Comput. Biol. 2007, 3, 199-213
23. Golosov, A. A.; Warren, J. J.; Beese, L. S.; Karplus, M. The Mechanism of the Translocation Step in DNA Replication by DNA Polymerase I: A Computer Simulation Analysis Structure 2010, 18, 83-93
24. Ma, J. P. Usefulness and Limitations of Normal Mode Analysis in Modeling Dynamics of Biomolecular Complexes Structure 2005, 13, 373-380
25. Lopez-Blanco, J. R.; Garzon, J. I.; Chacon, P. iMod: Multipurpose Normal Mode Analysis in Internal Coordinates Bioinformatics 2011, 27, 2843-2850
26. Yang, Z.; Majek, P.; Bahar, I. Allosteric Transitions of Supramolecular Systems Explored by Network Models: Application to Chaperonin GroEL PLoS Comput. Biol. 2009, 5, e1000360
27. 1-ATPase J. Mol. Biol. 2004, 340, 345-372
28. Kumar, S.; Bouzida, D.; Swendsen, R. H.; Kollman, P. A.; Rosenberg, J. M. The Weighted Histogram Analysis Method for Free-Energy Calculations on Biomolecules 0.1. The Method J. Comput. Chem. 1992, 13, 1011-1021
29. Kumar, S.; Rosenberg, J. M.; Bouzida, D.; Swendsen, R. H.; Kollman, P. A. Multidimensional Free-Energy Calculations Using the Weighted Histogram Analysis Method J. Comput. Chem. 1995, 16, 1339-1350
30. Müller, C.; Schlauderer, G.; Reinstein, J.; Schulz, G. Adenylate Kinase Motions during Catalysis: An Energetic Counterweight Balancing Substrate Binding Structure 1996, 4, 147-156
31. 5A Refined at 1.9 Å Resolution: A Model for a Catalytic Transition State J. Mol. Biol. 1992, 224, 159-177
32. Kuboniwa, H.; Tjandra, N.; Grzesiek, S.; Ren, H.; Klee, C. B.; Bax, A. Solution Structure of Calcium-Free Calmodulin Nat. Struct. Biol. 1995, 2, 768-776
33. Chattopadhyaya, R.; Meador, W. E.; Means, A. R.; Quiocho, F. A. Calmodulin Structure Refined at 1.7 Å Resolution J. Mol. Biol. 1992, 228, 1177-1192
34. Wang, Z.; Harkins, P. C.; Ulevitch, R. J.; Han, J.; Cobb, M. H.; Goldsmith, E. J. The Structure of Mitogen-Activated Protein Kinase P38 at 2.1-Å Resolution Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 2327-2332
35. Gill, A. L.; Frederickson, M.; Cleasby, A.; Woodhead, S. J.; Carr, M. G.; Woodhead, A. J.; Walker, M. T.; Congreve, M. S.; Devine, L. A.; Tisi, D. Identification of Novel p38α MAP Kinase Inhibitors Using Fragment-Based Lead Generation J. Med. Chem. 2005, 48, 414-426
36. Marques, O.; Sanejouand, Y. H. Hinge-Bending Motion in Citrate Synthase Arising from Normal Mode Calculations Proteins 1995, 23, 557-560
37. Duan, Y.; Wu, C.; Chowdhury, S.; Lee, M. C.; Xiong, G.; Zhang, W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T. A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations J. Comput. Chem. 2003, 24, 1999-2012
38. 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
39. Kondo, H. X.; Okimoto, N.; Morimoto, G.; Taiji, M. Free-Energy Landscapes of Protein Domain Movements upon Ligand Binding J. Phys. Chem. B 2011, 115, 7629-7636
40. Cui, W.; Cheng, Y.-H.; Geng, L.-L.; Liang, D.-S.; Hou, T.-J.; Ji, M.-J. Unraveling the Allosteric Inhibition Mechanism of PTP1B by Free Energy Calculation Based on Umbrella Sampling J. Chem. Inf. Model. 2013, 53, 1157-1167
41. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of Simple Potential Functions for Simulating Liquid Water J. Chem. Phys. 1983, 79, 926-935
42. Ryckaert, J.-P.; Ciccotti, G.; Berendsen, H. J. Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n -Alkanes J. Chem. Phys. 1977, 23, 327-341
43. Darden, T.; York, D.; Pedersen, L. Particle Mesh Ewald: An N ·log (N) Method for Ewald Sums in Large Systems J. Chem. Phys. 1993, 98, 10089
44. Case, D. A.; Darden, T. A; Cheatham, T. E., III; Simmerling, C. L.; Wang, J.; Duke, R. E; Luo, R.; Crowley, M.; Walker, R. C.; Zhang, W.; AMBER10; University of California: San Francisco, 2008.
45. Arora, K.; Brooks, C. L. Large-Scale Allosteric Conformational Transitions of Adenylate Kinase Appear to Involve a Population-Shift Mechanism Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 18496-18501
46. Hanson, J. A.; Duderstadt, K.; Watkins, L. P.; Bhattacharyya, S.; Brokaw, J.; Chu, J.-W.; Yang, H. Illuminating the Mechanistic Roles of Enzyme Conformational Dynamics Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 18055-18060
47. Henzler-Wildman, K. A.; Thai, V.; Lei, M.; Ott, M.; Wolf-Watz, M.; Fenn, T. Intrinsic Motions along an Enzymatic Reaction Trajectory Nature 2007, 450, 838-844
48. Marcus, R. A.; Sutin, N. Electron Transfers in Chemistry and Biology Biochim. Biophys. Acta 1985, 811, 265-322
49. Bae, E.; Phillips, G. N. Structures and Analysis of Highly Homologous Psychrophilic, Mesophilic, and Thermophilic Adenylate Kinases J. Biol. Chem. 2004, 279, 28202-28208
50. Matsunaga, Y.; Fujisaki, H.; Terada, T.; Furuta, T.; Moritsugu, K.; Kidera, A. Minimum Free Energy Path of Ligand-Induced Transition in Adenylate Kinase PLoS Comput. Biol. 2012, 8, e1002555
51. Wolf-Watz, M.; Thai, V.; Henzler-Wildman, K.; Hadjipavlou, G.; Eisenmesser, E. Z.; Kern, D. Linkage between Dynamics and Catalysis in a Thermophilic-Mesophilic Enzyme Pair Nat. Struct. Mol. Biol. 2004, 11, 945-949
52. Whitford, P. C.; Miyashita, O.; Levy, Y.; Onuchic, J. N. Conformational Transitions of Adenylate Kinase: Switching by Cracking J. Mol. Biol. 2007, 366, 1661-1671
53. Adkar, B. V.; Jana, B.; Bagchi, B. Role of Water in the Enzymatic Catalysis: Study of ATP + AMP → 2ADP Conversion by Adenylate Kinase J. Phys. Chem. A 2011, 115, 3691-3697
54. Chin, D.; Means, A. R. Calmodulin: A Prototypical Calcium Sensor Trends Cell Biol. 2000, 10, 322-328
55. Grabarek, Z. Structure of a Trapped Intermediate of Calmodulin: Calcium Regulation of EF-hand Proteins from a New Perspective J. Mol. Biol. 2005, 346, 1351-1366
56. Chen, B. W.; Lowry, D. F.; Mayer, M. U.; Squier, T. C. Helix A Stabilization Precedes Amino-terminal Lobe Activation upon Calcium Binding to Calmodulin Biochemistry 2008, 47, 9220-9226
57. Gsponer, J.; Christodoulou, J.; Cavalli, A.; Bui, J. M.; Richter, B.; Dobson, C. M.; Vendruscolo, M. A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction Structure 2008, 16, 736-746
58. Zhang, M.; Abrams, C.; Wang, L. P.; Gizzi, A.; He, L. P.; Lin, R. H.; Chen, Y.; Loll, P. J.; Pascal, J. M.; Zhang, J. F. Structural Basis for Calmodulin as a Dynamic Calcium Sensor Structure 2012, 20, 911-923
59. Wu, G. R.; Gao, Z. Y.; Dong, A. C.; Yu, S. N. Calcium-Induced Changes in Calmodulin Structural Dynamics and Thermodynamics Int. J. Biol. Macromol. 2012, 50, 1011-1017
60. Evenas, J.; Forsen, S.; Malmendal, A.; Akke, M. Backbone Dynamics and Energetics of a Calmodulin Domain Mutant Exchanging between Closed and Open Conformations J. Mol. Biol. 1999, 289, 603-617
61. 2+-Calmodulin Reveals Flexible Hand-like Properties of Its Domains Nat. Struct. Biol. 2001, 8, 990-997
62. Masino, L.; Martin, S. R.; Bayley, P. M. Ligand Binding and Thermodynamic Stability of a Multidomain Protein, Calmodulin Protein Sci. 2000, 9, 1519-1529
63. Rabl, C. R.; Martin, S. R.; Neumann, E.; Bayley, P. M. Temperature Jump Kinetic Study of the Stability of Apo-Calmodulin Biophys. Chem. 2002, 101-102, 553-564
64. Kumar, S.; Boehm, J.; Lee, J. C. P38 MAP Kinases: Key Signalling Molecules as Therapeutic Targets for Inflammatory Diseases Nat. Rev. Drug Discovery 2003, 2, 717-726
65. Pargellis, C.; Tong, L.; Churchill, L.; Cirillo, P. F.; Gilmore, T.; Graham, A. G.; Grob, P. M.; Hickey, E. R.; Moss, N.; Pav, S.; Regan, J. Inhibition of P38 MAP Kinase by Utilizing a Novel Allosteric Binding Site Nat. Struct. Biol. 2002, 9, 268-272
66. Regan, J.; Breitfelder, S.; Cirillo, P.; Gilmore, T.; Graham, A. G.; Hickey, E.; Klaus, B.; Madwed, J.; Moriak, M.; Moss, N. Pyrazole Urea-Based Inhibitors of P38 MAP Kinase: From Lead Compound to Clinical Candidate J. Med. Chem. 2002, 45, 2994-3008
67. Huang, Y. M. M.; Chen, W.; Potter, M. J.; Chang, C. E. A. Insights from Free-Energy Calculations: Protein Conformational Equilibrium, Driving Forces, and Ligand-Binding Modes Biophys. J. 2012, 103, 342-351
68. Lovera, S.; Sutto, L.; Boubeva, R.; Scapozza, L.; Dolker, N.; Gervasio, F. L. The Different Flexibility of c-Src and c-Abl Kinases Regulates the Accessibility of a Druggable Inactive Conformation J. Am. Chem. Soc. 2012, 134, 2496-2499
69. Berteotti, A.; Cavalli, A.; Branduardi, D.; Gervasio, F. L.; Recanatini, M.; Parrinello, M. Protein Conformational Transitions: The Closure Mechanism of a Kinase Explored by Atomistic Simulations J. Am. Chem. Soc. 2009, 131, 244-250
70. Gan, W. X.; Yang, S. C.; Roux, B. Atomistic View of the Conformational Activation of Src Kinase Using the String Method with Swarms-of-Trajectories Biophys. J. 2009, 97, L8-L10
71. Filomia, F.; De Rienzo, F.; Menziani, M. C. Insights into MAPK P38α DFG Flip Mechanism by Accelerated Molecular Dynamics Bioorgan. Med. Chem. 2010, 18, 6805-6812
72. Shan, Y. B.; Seeliger, M. A.; Eastwood, M. P.; Frank, F.; Xu, H. F.; Jensen, M. O.; Dror, R. O.; Kuriyan, J.; Shaw, D. E. A Conserved Protonation-Dependent Switch Controls Drug Binding in the Abl Kinase Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 139-144
73. Kottalam, J.; Case, D. Langevin Modes of Macromolecules: Applications to Crambin and DNA Hexamers Biopolymers 1990, 29, 1409-1421
74. Hayward, J. A.; Smith, J. C. Temperature Dependence of Protein Dynamics: Computer Simulation Analysis of Neutron Scattering Properties Biophys. J. 2002, 82, 1216-1225
75. Levy, R.; Srinivasan, A.; Olson, W.; McCammon, J. Quasi-Harmonic Method for Studying very Low Frequency Modes in Proteins Biopolymers 1984, 23, 1099-1112
76. Hayward, S.; Kitao, A.; GoÌ..., N. Harmonicity and Anharmonicity in Protein Dynamics: A Normal Mode Analysis and Principal Component Analysis Proteins 1995, 23, 177-186
77. Hayward, S.; Kitao, A.; GoÌ..., N. Harmonic and Anharmonic Aspects in the Dynamics of BPTI: A Normal Mode Analysis and Principal Component Analysis Protein Sci. 1994, 3, 936-943
78. Hayward, S.; Go, N. Collective Variable Description of Native Protein Dynamics Annu. Rev. Phys. Chem. 1995, 46, 223-250
79. Kitao, A.; GoÌ..., N. Conformational Dynamics of Polypeptides and Proteins in the Dihedral Angle Space and in the Cartesian Coordinate Space: Normal Mode Analysis of deca-Alanine J. Comput. Chem. 1991, 12, 359-368
80. Zheng, W. Anharmonic Normal Mode Analysis of Elastic Network Model Improves the Modeling of Atomic Fluctuations in Protein Crystal Structures Biophys. J. 2010, 98, 3025-3034
81. Vogtherr, M.; Saxena, K.; Hoelder, S.; Grimme, S.; Betz, M.; Schieborr, U.; Pescatore, B.; Robin, M.; Delarbre, L.; Langer, T. NMR Characterization of Kinase P38 Dynamics in Free and Ligand-bound Forms Angew. Chem., Int. Ed. 2006, 45, 993-997