Conformation Prediction of Human Plasmin and Docking on Gold Nanoparticle
Plasmin plays an important role in the human
circulatory system owing to its catalytic ability of fibrinolysis. The
immediate injection of plasmin in patients of strokes has intrigued
many scientists to design vectors that can transport plasmin to the
desired location in human body. Here we predict the structure of
human plasmin and investigate the interaction of plasmin with the
gold-nanoparticle.
Because the crystal structure of plasminogen has been solved, we
deleted N-terminal domain (Pan-apple domain) of plasminogen and
generate a mimic of the active form of this enzyme (plasmin). We
conducted a simulated annealing process on plasmin and discovered a
very large conformation occurs. Kringle domains 1, 4 and 5 had been
observed to leave its original location relative to the main body of the
enzyme and the original doughnut shape of this enzyme has been
transformed to a V-shaped by opening its two arms. This observation
of conformational change is consistent with the experimental results of
neutron scattering and centrifugation.
We subsequently docked the plasmin on the simulated gold surface
to predict their interaction. The V-shaped plasmin could utilize its
Kringle domain and catalytic domain to contact the gold surface.
Our findings not only reveal the flexibility of plasmin structure but
also provide a guide for the design of a plasmin-gold nanoparticle.
[1] Ramakrishnan V, Patthy L, Mangel WF. Conformation of
Lys-plasminogen and the kringle 1-3 fragment of plasminogen analyzed
by small-angle neutron scattering. Biochemistry. 1991; 30:3963-9.
[2] Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ,
Encarnacao JA, et al. The X-ray Crystal Structure of Full-Length Human
Plasminogen. Cell reports. 2012; 1:185-90.
[3] Xue Y, Bodin C, Olsson K. Crystal structure of the native plasminogen
reveals an activation-resistant compact conformation. Journal of
thrombosis and haemostasis: JTH. 2012; 10:1385-96.
[4] Pronk S, Pall S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, et al.
GROMACS 4.5: a high-throughput and highly parallel open source
molecular simulation toolkit. Bioinformatics. 2013; 29:845-54.
[5] Brancolini G, Kokh DB, Calzolai L, Wade RC, Corni S. Docking of
ubiquitin to gold nanoparticles. ACS nano. 2012; 6:9863-78.
[6] Hoefling M, Monti S, Corni S, Gottschalk KE. Interaction of beta-sheet
folds with a gold surface. PLoS One. 2011; 6:e20925.
[7] Stueker O, Ortega VA, Goss GG, Stepanova M. Understanding
interactions of functionalized nanoparticles with proteins: a case study on
lactate dehydrogenase. Small. 2014; 10:2006-21.
[8] Gabdoulline RR, Wade RC. Simulation of the diffusional association of
barnase and barstar. Biophys J. 1997; 72:1917-29.
[9] Gabdoulline RR, Wade RC. Brownian dynamics simulation of
protein-protein diffusional encounter. Methods. 1998; 14:329-41.
[1] Ramakrishnan V, Patthy L, Mangel WF. Conformation of
Lys-plasminogen and the kringle 1-3 fragment of plasminogen analyzed
by small-angle neutron scattering. Biochemistry. 1991; 30:3963-9.
[2] Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ,
Encarnacao JA, et al. The X-ray Crystal Structure of Full-Length Human
Plasminogen. Cell reports. 2012; 1:185-90.
[3] Xue Y, Bodin C, Olsson K. Crystal structure of the native plasminogen
reveals an activation-resistant compact conformation. Journal of
thrombosis and haemostasis: JTH. 2012; 10:1385-96.
[4] Pronk S, Pall S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, et al.
GROMACS 4.5: a high-throughput and highly parallel open source
molecular simulation toolkit. Bioinformatics. 2013; 29:845-54.
[5] Brancolini G, Kokh DB, Calzolai L, Wade RC, Corni S. Docking of
ubiquitin to gold nanoparticles. ACS nano. 2012; 6:9863-78.
[6] Hoefling M, Monti S, Corni S, Gottschalk KE. Interaction of beta-sheet
folds with a gold surface. PLoS One. 2011; 6:e20925.
[7] Stueker O, Ortega VA, Goss GG, Stepanova M. Understanding
interactions of functionalized nanoparticles with proteins: a case study on
lactate dehydrogenase. Small. 2014; 10:2006-21.
[8] Gabdoulline RR, Wade RC. Simulation of the diffusional association of
barnase and barstar. Biophys J. 1997; 72:1917-29.
[9] Gabdoulline RR, Wade RC. Brownian dynamics simulation of
protein-protein diffusional encounter. Methods. 1998; 14:329-41.
@article{"International Journal of Medical, Medicine and Health Sciences:70067", author = "Wen-Shyong Tzou and Chih-Ching Huang and Chin-Hwa Hu and Ying-Tsang Lo and Tun-Wen Pai and Chia-Yin Chiang and Chung-Hao Li and Hong-Jyuan Jian", title = "Conformation Prediction of Human Plasmin and Docking on Gold Nanoparticle", abstract = "Plasmin plays an important role in the human
circulatory system owing to its catalytic ability of fibrinolysis. The
immediate injection of plasmin in patients of strokes has intrigued
many scientists to design vectors that can transport plasmin to the
desired location in human body. Here we predict the structure of
human plasmin and investigate the interaction of plasmin with the
gold-nanoparticle.
Because the crystal structure of plasminogen has been solved, we
deleted N-terminal domain (Pan-apple domain) of plasminogen and
generate a mimic of the active form of this enzyme (plasmin). We
conducted a simulated annealing process on plasmin and discovered a
very large conformation occurs. Kringle domains 1, 4 and 5 had been
observed to leave its original location relative to the main body of the
enzyme and the original doughnut shape of this enzyme has been
transformed to a V-shaped by opening its two arms. This observation
of conformational change is consistent with the experimental results of
neutron scattering and centrifugation.
We subsequently docked the plasmin on the simulated gold surface
to predict their interaction. The V-shaped plasmin could utilize its
Kringle domain and catalytic domain to contact the gold surface.
Our findings not only reveal the flexibility of plasmin structure but
also provide a guide for the design of a plasmin-gold nanoparticle.", keywords = "Docking, gold nanoparticle, molecular simulation,
plasmin.", volume = "9", number = "6", pages = "488-4", }