Next Article in Journal
Posttranslational Modifications of GLUT4 Affect Its Subcellular Localization and Translocation
Next Article in Special Issue
Design, Synthesis, Biological Activity and Molecular Dynamics Studies of Specific Protein Tyrosine Phosphatase 1B Inhibitors over SHP-2
Previous Article in Journal
Cationic Antimicrobial Polymers and Their Assemblies
Article

Molecular Dynamics Simulation of Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative Inhibitors

by 1,†, 2,†, 1,*, 2, 1 and 1,*
1
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
2
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2013, 14(5), 9947-9962; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms14059947
Received: 28 March 2013 / Revised: 27 April 2013 / Accepted: 6 May 2013 / Published: 10 May 2013
Serotonin is a neurotransmitter that modulates many central and peripheral functions. Tryptophan hydroxylase-1 (TPH1) is a key enzyme of serotonin synthesis. In the current study, the interaction mechanism of phenylalanine derivative TPH1 inhibitors was investigated using molecular dynamics (MD) simulations, free energy calculations, free energy decomposition analysis and computational alanine scanning. The predicted binding free energies of these complexes are consistent with the experimental data. The analysis of the individual energy terms indicates that although the van der Waals and electrostatics interaction contributions are important in distinguishing the binding affinities of these inhibitors, the electrostatic contribution plays a more crucial role in that. Moreover, it is observed that different configurations of the naphthalene substituent could form different binding patterns with protein, yet lead to similar inhibitory potency. The combination of different molecular modeling techniques is an efficient way to interpret the interaction mechanism of inhibitors and our work could provide valuable information for the TPH1 inhibitor design in the future. View Full-Text
Keywords: tryptophan hydroxylase; phenylalanine derivative; molecular dynamics simulation; MM/GBSA tryptophan hydroxylase; phenylalanine derivative; molecular dynamics simulation; MM/GBSA
Show Figures

MDPI and ACS Style

Zhong, H.; Huang, W.; He, G.; Peng, C.; Wu, F.; Ouyang, L. Molecular Dynamics Simulation of Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative Inhibitors. Int. J. Mol. Sci. 2013, 14, 9947-9962. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms14059947

AMA Style

Zhong H, Huang W, He G, Peng C, Wu F, Ouyang L. Molecular Dynamics Simulation of Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative Inhibitors. International Journal of Molecular Sciences. 2013; 14(5):9947-9962. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms14059947

Chicago/Turabian Style

Zhong, Hao, Wei Huang, Gu He, Cheng Peng, Fengbo Wu, and Liang Ouyang. 2013. "Molecular Dynamics Simulation of Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative Inhibitors" International Journal of Molecular Sciences 14, no. 5: 9947-9962. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms14059947

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop