title: Structure-based design of carbon nanotubes as HIV-1 protease inhibitors: atomistic and coarse-grained simulations.
abstract: Nanoparticles such as fullerenes and carbon nanotubes have been extensively studied for biomedical applications. In this paper, we report the design of carbon nanotubes as HIV-1 protease inhibitors. Docking and molecular dynamics calculations are performed using an atomistic model to explore the optimal interaction structure and free energy between the nanotube and HIV-1 protease. A coarse-grained model is then developed based on the atomistic model, allowing us to investigate the dynamic behaviors of the protease in the bound and unbound states. The dynamic process reveals that the carbon nanotube is able to bind to the active site of the protease and prevent the active flaps from opening up, thus blocking the function of the protease. This process is strongly influenced by the size of the nanotube. The binding of carbon nanotubes to an alternative binding site other than the active site is also explored. Therefore, carbon nanotube-based inhibitors have great potential for application as HIV-1 protease inhibitors.
authors.affiliation: Institute of High Performance Computing, 1 Fusionopolis Way, #16-16 Connexis, Singapore 138632, Singapore. chengy@ihpc.a-star.edu.sg
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Dechang
authors.initials: D
authors.lastname: Li
authors.forename: Baohua
authors.initials: B
authors.lastname: Ji
authors.forename: Xinghua
authors.initials: X
authors.lastname: Shi
authors.forename: Huajian
authors.initials: H
authors.lastname: Gao
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010316:Particle Size; D013816:Thermodynamics
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D037742:Nanotubes, Carbon; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1