Citation: Li-Rong Zheng, Liang Hong. Combining Neutron Scattering, Deuteration Technique, and Molecular Dynamics Simulations to Study Dynamics of Protein and Its Surface Water Molecules[J]. Chinese Journal of Polymer Science, ;2019, 37(11): 1083-1091. doi: 10.1007/s10118-019-2312-2 shu

Combining Neutron Scattering, Deuteration Technique, and Molecular Dynamics Simulations to Study Dynamics of Protein and Its Surface Water Molecules

Li-Rong Zheng ^a,b ,
Liang Hong ^a,b,,

a.
School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China
b.
Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China

Corresponding author: Liang Hong, hongl3liang@sjtu.edu.cn
Received Date: 14 April 2019
Revised Date: 18 May 2019
Available Online: 2 September 2019

Protein internal dynamics is essential for its function. Exploring the internal dynamics of protein molecules as well as its connection to protein structure and function is a central topic in biophysics. However, the atomic motions in protein molecules exhibit a great degree of complexities. These complexities arise from the complex chemical composition and superposition of different types of atomic motions on the similar time scales, and render it challenging to explicitly understand the microscopic mechanism governing protein motions, functions, and their connections. Here, we demonstrate that, by using neutron scattering, molecular dynamics simulation, and deuteration technique, one can address this challenge to a large extent.
- Neutron scattering,
- Deuteration techniques,
- Molecular dynamics simulations,
- Protein,
- Hydration water,
- Dynamics
1. [1]
  Johs, A.; Harwood, I. M.; Parks, J. M.; Nauss, R. E.; Smith, J. C.; Liang, L.; Miller, S. M. Structural characterization of intramolecular Hg²⁺ transfer between flexibly linked domains of mercuric ion reductase. J. Mol. Biol. 2011, 413 (3), 639-656. doi: 10.1016/j.jmb.2011.08.042
2. [2]
  Martin, G. S. The hunting of the Src. Nat. Rev. Mol. Cell. Biol. 2001, 2 (5), 47-47. doi: 10.1038/35073094
3. [3]
  Banks, R. D.; Blake, C. C.; Evans, P. R.; Haser, R., .; Rice, D. W.; Hardy, G. W.; Merrett, M., .; Phillips, A. W. Sequence, structure and activity of phosphoglycerate kinase: a possible hinge-bending enzyme. Nature 1979, 279 (5716), 773-777. doi: 10.1038/279773a0
4. [4]
  Rupley, J. A.; Careri, G. Protein hydration and function. In Advances in protein chemistry. Elsevier, 1991, Vol. 41, p. 37−172
5. [5]
  Bellissent-Funel, M. C.; Hassanali, A.; Havenith, M.; Henchman, R.; Pohl, P.; Sterpone, F.; Van, d. S. D.; Xu, Y.; Garcia, A. E. Water determines the structure and dynamics of proteins. Chem. Rev. 2016, 116 (13), 7673-7679. doi: 10.1021/acs.chemrev.5b00664
6. [6]
  Hans, F.; Guo, C.; Joel, B.; Fenimore, P. W.; Helén, J.; Mcmahon, B. H.; Stroe, I. R.; Jan, S.; Young, R. D. A unified model of protein dynamics. Proc. Natl. Acad. Sci. USA 2009, 106 (13), 5129-5134. doi: 10.1073/pnas.0900336106
7. [7]
  Biman, B. Water dynamics in the hydration layer around proteins and micelles. Chem. Rev. 2005, 105 (9), 3197-3219. doi: 10.1021/cr020661+
8. [8]
  Philip, B. Water and life: seeking the solution. Nature 2005, 436 (7054), 1084. doi: 10.1038/4361084a
9. [9]
  Pocker, Y. Water in enzyme reactions: Biophysical aspects of hydration-dehydration processes. CMLS, Cell. Mol. Life Sci. 2000, 57 (7), 1008-1017. doi: 10.1007/PL00000741
10. [10]
  Jian, P.; Todd, S.; Ning, Z.; Catterall, W. A. The crystal structure of a voltage-gated sodium channel. Nature 2011, 475 (7356), 353-358. doi: 10.1038/nature10238
11. [11]
  Pawlus, S.; Khodadadi, S.; Sokolov, A. P. Conductivity in hydrated proteins: no signs of the fragile-to-strong crossover. Phys. Rev. Lett. 2008, 100 (10), 2197-2204.
12. [12]
  Otting, G.; Liepinsh, E.; Wuthrich, K. Protein hydration in aqueous solution. Science 1991, 254 (5034), 974-980. doi: 10.1126/science.1948083
13. [13]
  Valeria, C. N.; Martina, H. New insights into the role of water in biological function: studying solvated biomolecules using terahertz absorption spectroscopy in conjunction with molecular dynamics simulations. J. Am. Chem. Soc. 2014, 136 (37), 12800-12807. doi: 10.1021/ja504441h
14. [14]
  Yang, J.; Wang, Y.; Wang, L.; Zhong, D. Mapping hydration dynamics around a β-barrel protein. J. Am. Chem. Soc. 2017, 139 (12), 4399-4408. doi: 10.1021/jacs.6b12463
15. [15]
  Chen, C.; Stevens, B.; Kaur, J.; Cabral, D.; Liu, H.; Wang, Y.; Zhang, H.; Rosenblum, G.; Smilansky, Z.; Goldman, Y. E. Single-molecule fluorescence measurements of ribosomal translocation dynamics. Mol. Cell 2011, 42 (3), 367-377. doi: 10.1016/j.molcel.2011.03.024
16. [16]
  Hong, L.; Jain, N.; Cheng, X.; Bernal, A.; Tyagi, M.; Smith, J. C. Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering. Sci. Adv. 2016, 2 (10), e1600886. doi: 10.1126/sciadv.1600886
17. [17]
  Hong, L.; Sharp, M. A.; Poblete, S.; Biehl, R.; Zamponi, M.; Szekely, N.; Appavou, M. S.; Winkler, R. G.; Nauss, R. E.; Johs, A.; Parks, J. M.; Yi, Z.; Cheng, X.; Liang, L.; Ohl, M.; Miller, S. M.; Richter, D.; Gompper, G.; Smith, J. C. Structure and dynamics of a compact state of a multidomain protein, the mercuric ion reductase. Biophys. J. 2014, 107 (2), 393-400. doi: 10.1016/j.bpj.2014.06.013
18. [18]
  Hong, L.; Smolin, N.; Lindner, B.; Sokolov, A. P.; Smith, J. C. Three classes of motion in the dynamic neutron-scattering susceptibility of a globular protein. Phys. Rev. Lett. 2011, 107 (14), 148102. doi: 10.1103/PhysRevLett.107.148102
19. [19]
  Hong, L.; Smolin, N.; Smith, J. C. de Gennes narrowing describes the relative motion of protein domains. Phys. Rev. Lett. 2014, 112 (15), 158102. doi: 10.1103/PhysRevLett.112.158102
20. [20]
  Liu, Z.; Huang, J.; Tyagi, M.; O'Neill, H.; Zhang, Q.; Mamontov, E.; Jain, N.; Wang, Y.; Zhang, J.; Smith, J. C.; Hong, L. Dynamical transition of collective motions in dry proteins. Phys. Rev. Lett. 2017, 119 (4), 048101. doi: 10.1103/PhysRevLett.119.048101
21. [21]
  Nickels, J. D.; O'Neill, H.; Hong, L.; Tyagi, M.; Ehlers, G.; Weiss, K. L.; Zhang, Q.; Yi, Z.; Mamontov, E.; Smith, J. C.; Sokolov, A. P. Dynamics of protein and its hydration water: neutron scattering studies on fully deuterated GFP. Biophys. J. 2012, 103 (7), 1566-1575. doi: 10.1016/j.bpj.2012.08.046
22. [22]
  Tan, P.; Liang, Y.; Xu, Q.; Mamontov, E.; Li, J.; Xing, X.; Hong, L. Gradual crossover from subdiffusion to normal diffusion: a many-body effect in protein surface water. Phys. Rev. Lett. 2018, 120 (24), 248101. doi: 10.1103/PhysRevLett.120.248101
23. [23]
  Hong, L.; Cheng, X.; Glass, D. C.; Smith, J. C. Surface hydration amplifies single-well protein atom diffusion propagating into the macromolecular core. Phys. Rev. Lett. 2012, 108 (23), 238102. doi: 10.1103/PhysRevLett.108.238102
24. [24]
  Hong, L.; Glass, D. C.; Nickels, J. D.; Perticaroli, S.; Yi, Z.; Tyagi, M.; O'Neill, H.; Zhang, Q.; Sokolov, A. P.; Smith, J. C. Elastic and conformational softness of a globular protein. Phys. Rev. Lett. 2013, 110 (2), 028104. doi: 10.1103/PhysRevLett.110.028104
25. [25]
  Liu, Z.; Yang, C.; Huang, J.; Ciampalini, G.; Li, J.; García Sakai, V.; Tyagi, M.; O’Neill, H.; Zhang, Q.; Capaccioli, S.; Ngai, K. L.; Hong, L. Direct experimental characterization of contributions from self-motion of hydrogen and from interatomic motion of heavy atoms to protein anharmonicity. J. Phys. Chem. B 2018, 122 (43), 9956-9961. doi: 10.1021/acs.jpcb.8b09355
26. [26]
  Liu, Z.; Lemmonds, S.; Huang, J.; Tyagi, M.; Hong, L.; Jain, N. Entropic contribution to enhanced thermal stability in the thermostable P450 CYP119. Proc. Natl. Acad. Sci. USA 2018, 115 (43), E10049-E10058. doi: 10.1073/pnas.1807473115
27. [27]
  Buchenau, U.; Wischnewski, A.; Richter, D.; Frick, B. Is the fast process at the glass transition mainly due to long wavelength excitations? Phys. Rev. Lett. 1996, 77 (19), 4035-4038. doi: 10.1103/PhysRevLett.77.4035
28. [28]
  Nickels, J. D.; Perticaroli, S.; O'Neill, H.; Zhang, Q.; Ehlers, G.; Sokolov, A. P. Coherent neutron scattering and collective dynamics in the protein, GFP. Biophys. J. 2013, 105 (9), 2182-2187. doi: 10.1016/j.bpj.2013.09.029
29. [29]
  Carpenter, J. M.; Pelizzari, C. A. Inelastic neutron scattering from amorphous solids. I. Calculation of the scattering law for model structures. Phys. Rev. B 1975, 12, 2391. doi: 10.1103/PhysRevB.12.2391
30. [30]
  Suhre, K.; Sanejouand, Y. H. ElNemo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement. Nucleic Acids Res. 2004, 32 (suppl_2, 1), W610-W614.
31. [31]
  Khodadadi, S.; Pawlus, S.; Sokolov, A. P. Influence of hydration on protein dynamics: Combining dielectric and neutron scattering spectroscopy data. J. Phys. Chem. B 2008, 112 (45), 14273-14280. doi: 10.1021/jp8059807
32. [32]
  Modig, K.; Liepinsh, E.; Otting, G.; Halle, B. Dynamics of protein and peptide hydration. J. Am. Chem. Soc. 2004, 126 (1), 102-114. doi: 10.1021/ja038325d
33. [33]
  Ebbinghaus, S.; Kim, S. J.; Heyden, M.; Yu, X.; Heugen, U.; Gruebele, M.; Leitner, D. M.; Havenith, M. An extended dynamical hydration shell around proteins. Proc. Natl. Acad. Sci. USA 2007, 104 (52), 20749-20752. doi: 10.1073/pnas.0709207104
34. [34]
  King, J. T.; Kubarych, K. J. Site-specific coupling of hydration water and protein flexibility studied in solution with ultrafast 2D-IR spectroscopy. J. Am. Chem. Soc. 2012, 134 (45), 18705-18712. doi: 10.1021/ja307401r
35. [35]
  Vitkup, D.; Ringe, D.; Petsko, G. A.; Karplus, M. Solvent mobility and the protein 'glass' transition. Nat. Struct. Biol. 2000, 7 (1), 34-38. doi: 10.1038/71231
36. [36]
  Roh, J. H.; Curtis, J. E.; Azzam, S.; Novikov, V. N.; Peral, I.; Chowdhuri, Z.; Gregory, R. B.; Sokolov, A. P. Influence of hydration on the dynamics of lysozyme. Biophys. J. 2006, 91 (7), 2573-2588. doi: 10.1529/biophysj.106.082214
37. [37]
  Rasmussen, B. F.; Stock, A. M.; Ringe, D.; Petsko, G. A. Crystalline ribonuclease-a Loses function below the dynamic transition at 220 K. Nature 1992, 357 (6377), 423-424. doi: 10.1038/357423a0
38. [38]
  He, Y.; Ku, P. I.; Knab, J. R.; Chen, J. Y.; Markelz, A. G. Protein dynamical transition does not require protein structure. Phys. Rev. Lett. 2008, 101 (17), 178103. doi: 10.1103/PhysRevLett.101.178103
39. [39]
  Ferrand, M.; Dianoux, A. J.; Petry, W.; Zaccaï, G. Thermal motions and function of bacteriorhodopsin in purple membranes: effects of temperature and hydration studied by neutron scattering. Proc. Natl. Acad. Sci. USA 1993, 90 (20), 9668-9672. doi: 10.1073/pnas.90.20.9668
1. [1]
  Zhimin Song , Zhe Tang , Yu Zhang , Yanru Zhou , Xiaozheng Duan , Yan Du , Chong-Bo Ma . DNA-modulated Mo-Zn single-atom nanozymes: Insights from molecular dynamics simulations to smartphone-assisted biosensing. Chinese Chemical Letters, 2025, 36(10): 110680-. doi: 10.1016/j.cclet.2024.110680
2. [2]
  Dongmei Yao , Junsheng Zheng , Liming Jin , Xiaomin Meng , Zize Zhan , Runlin Fan , Cong Feng , Pingwen Ming . Effect of surface oxidation on the interfacial and mechanical properties in graphite/epoxy composites composite bipolar plates. Chinese Chemical Letters, 2024, 35(11): 109382-. doi: 10.1016/j.cclet.2023.109382
3. [3]
  Yuhao Zhou , Siyuan Wu , Xiaozhe Ren , Hongjin Li , Shu Li , Tianying Yan . Effects of salt fraction on the Na⁺ transport in salt-in-ionic liquid electrolytes. Chinese Chemical Letters, 2025, 36(6): 110048-. doi: 10.1016/j.cclet.2024.110048
4. [4]
  Jinqi Yang , Xiaoxiang Hu , Yuanyuan Zhang , Lingyu Zhao , Chunlin Yue , Yuan Cao , Yangyang Zhang , Zhenwen Zhao . Direct observation of natural products bound to protein based on UHPLC-ESI-MS combined with molecular dynamics simulation. Chinese Chemical Letters, 2025, 36(5): 110128-. doi: 10.1016/j.cclet.2024.110128
5. [5]
  Hongqin Chu , Liyang Li , Fan Yang , Shujuan Li , Jiayao Wang , Shulai Lei , Jinbo Sun , Ke Xu , Xinyue Xiong , Zhenpeng Hu . Characterization of intrinsic defects and their effects on carrier lifetime in CdTeSe: First principles and non-adiabatic molecular dynamics simulations. Chinese Chemical Letters, 2026, 37(9): 111490-. doi: 10.1016/j.cclet.2025.111490
6. [6]
  Heng-Su Liu , Xi-Ming Zhang , Ge-Hao Liang , Shisheng Zheng , Jian-Feng Li . Investigation of water structure and proton transfer within confined graphene by ab initio molecule dynamics and multiscale data analysis. Chinese Journal of Structural Chemistry, 2025, 44(6): 100596-100596. doi: 10.1016/j.cjsc.2025.100596
7. [7]
  Yan Zhao , Zhenming Tian , Qisen Jia , Ting Yao , Jiashu Li , Yanan Wang , Xuejing Cui , Jing Liu , Xin Chen , Luhua Jiang . Crystal orientation dependent charge transfer dynamics and interfacial water configuration boosting photoelectrocatalytic water oxidation to H2O2. Chinese Journal of Structural Chemistry, 2025, 44(7): 100619-100619. doi: 10.1016/j.cjsc.2025.100619
8. [8]
  Kangren Kong , Zaiqiang Ma , Yu Yin , Zhaoming Liu , Ruikang Tang . Nuclear magnetic resonance-guided Monte Carlo/molecular dynamics structure inference for amorphous solids. Chinese Journal of Structural Chemistry, 2026, 45(3): 100773-100773. doi: 10.1016/j.cjsc.2025.100773
9. [9]
  Shiyang Sun , Ning Yang , Yaqiu Mao , Ting Wei , Pengli Wei , Tingting Yang , Yixin Zhang , Jian Yan , Changkai Jia , Yi Li , Xu Cai , Zhiyuan Zhao , Xuesong Feng , Xiaomei Zhuang , Wenpeng Zhang , Junhai Xiao , Pengyun Li , Zhibing Zheng , Song Li . Rational design of VHL-recruiting KRAS^G12C proteolysis-targeting chimeras based on molecular dynamics simulation. Chinese Chemical Letters, 2026, 37(2): 110992-. doi: 10.1016/j.cclet.2025.110992
10. [10]
  Xinyi Hong , Tailing Xue , Zhou Xu , Enrong Xie , Mingkai Wu , Qingqing Wang , Lina Wu . Non-Site-Specific Fluorescent Labeling of Proteins as a Chemical Biology Experiment. University Chemistry, 2024, 39(4): 351-360. doi: 10.3866/PKU.DXHX202310010
11. [11]
  Chenghao Ge , Peng Wang , Pei Yuan , Tai Wu , Rongjun Zhao , Rong Huang , Lin Xie , Yong Hua . Tuning hot carrier transfer dynamics by perovskite surface modification. Chinese Chemical Letters, 2024, 35(10): 109352-. doi: 10.1016/j.cclet.2023.109352
12. [12]
  Yan-Rui Zhao , Jin Zhang , Shi-Kun Yan , Guang-Zhi Zhou , Ya-Hui Wang , Qi-Yue Xin , Ji-Xiang Hu . Solvent-coordination directed control of electron transfer dynamics in photoactive complexes. Chinese Journal of Structural Chemistry, 2025, 44(12): 100753-100753. doi: 10.1016/j.cjsc.2025.100753
13. [13]
  Shiyu Hou , Maolin Sun , Liming Cao , Chaoming Liang , Jiaxin Yang , Xinggui Zhou , Jinxing Ye , Ruihua Cheng . Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor. Chinese Chemical Letters, 2024, 35(4): 108761-. doi: 10.1016/j.cclet.2023.108761
14. [14]
  Rongjun Zhao , Tai Wu , Yong Hua , Yude Wang . Improving performance of perovskite solar cells enabled by defects passivation and carrier transport dynamics regulation via organic additive. Chinese Chemical Letters, 2025, 36(2): 109587-. doi: 10.1016/j.cclet.2024.109587
15. [15]
  Aoxuan Song , Qinglong Qiao , Ning Xu , Yiyan Ruan , Wenhao Jia , Xiang Wang , Zhaochao Xu . Super-resolution imaging of cellular pseudopodia dynamics with a target-specific blinkogenic probe. Chinese Chemical Letters, 2025, 36(8): 110643-. doi: 10.1016/j.cclet.2024.110643
16. [16]
  Takuya Tanaka , Rikuto Noda , Yuki Sawatari , Riki Iwai , Ben Zhong Tang , Gen-ichi Konishi . Viscosity responsiveness of excited-state dynamics in aggregated-induced emission luminogens. Chinese Chemical Letters, 2025, 36(12): 111495-. doi: 10.1016/j.cclet.2025.111495
17. [17]
  Shujun Liu , Wenfeng Xu , Pengfei Jin , Li-Li Huang . Real-time monitoring of virus infection dynamics in established infection models for mechanism analysis. Chinese Chemical Letters, 2026, 37(4): 111076-. doi: 10.1016/j.cclet.2025.111076
18. [18]
  Hang Xu , Shijie Lu , Yike Song , Jiale Zhou , Bin Shen , Yejun Zou , Zhuo Zhang , Yuzheng Zhao , Huifeng Wang . Artificial intelligence-driven multimodal image analyzer for genetically encoded fluorescence sensors on cell division metabolism dynamics. Chinese Chemical Letters, 2026, 37(8): 111757-. doi: 10.1016/j.cclet.2025.111757
19. [19]
  Mengjia Luo , Yi Qiu , Zhengyang Zhou . Exploring temperature-driven phase dynamics of phosphate: The periodic to incommensurately modulated long-range ordered phase transition in CsCdPO4. Chinese Journal of Structural Chemistry, 2025, 44(1): 100446-100446. doi: 10.1016/j.cjsc.2024.100446
20. [20]
  Dongdong Liu , Ziqi Tang , Haoyu Wang , Xinjie Li , Jingyang Li , Chao Zhu , Shan Ding , Yuan-sheng Cheng , Hui Zhang , Peipei Li , Ju Wu , Guozan Yuan . Rational design of ZnIn2S4-COF heterojunction to inhibit photogenerated carrier dynamics for enhanced photocatalytic CO2 reduction. Chinese Journal of Structural Chemistry, 2026, 45(1): 100762-100762. doi: 10.1016/j.cjsc.2025.100762

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(2212)
HTML views(65)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142