title: Bio-mimicking of proline-rich motif applied to carbon nanotube reveals unexpected subtleties underlying nanoparticle functionalization.
abstract: Here, we report computational studies of the SH3 protein domain interacting with various single-walled carbon nanotubes (SWCNT) either bare or functionalized by mimicking the proline-rich motif (PRM) ligand (PPPVPPRR) and compare it to the SH3-PRM complex binding. With prolines or a single arginine attached, the SWCNT gained slightly on specificity when compared with the bare control, whereas with multi-arginine systems the specificity dropped dramatically to our surprise. Although the electrostatic interaction provided by arginines is crucial in the recognition between PRM and SH3 domain, our results suggest that attaching multiple arginines to the SWCNT has a detrimental effect on the binding affinity. Detailed analysis of the MD trajectories found two main factors that modulate the specificity of the binding: the existence of competing acidic patches at the surface of SH3 that leads to "trapping and clamping" by the arginines, and the rigidity of the SWCNT introducing entropic penalties in the proper binding. Further investigation revealed that the same "clamping" phenomenon exits in the PRM-SH3 system, which has not been reported in previous literature. The competing effects between nanoparticle and its functionalization components revealed by our model system should be of value to current and future nanomedicine designs.
authors.affiliation: Bio-X Lab, Department of Physics, and Soft Matter Research Center, Zhejiang University, Hangzhou 310027, China.
authors.forename: Yuanzhao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States.
authors.forename: Camilo A
authors.initials: CA
authors.lastname: Jimenez-Cruz
authors.affiliation: Bio-X Lab, Department of Physics, and Soft Matter Research Center, Zhejiang University, Hangzhou 310027, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bio-X Lab, Department of Physics, and Soft Matter Research Center, Zhejiang University, Hangzhou 310027, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 1] IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States [2] Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China [3] Department of Chemistry, Columbia University, New York, New York 10027, United States.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
mesh_terms: D001120:Arginine / Q000737:chemistry; D001665:Binding Sites / Q000502:physiology; D032701:Biomimetics / Q000379:methods; D008024:Ligands; D053758:Nanoparticles / Q000737:chemistry*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D055232:Proline-Rich Protein Domains / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D055672:Static Electricity; D018909:src Homology Domains / Q000502:physiology
chemical_list: D008024:Ligands; D037742:Nanotubes, Carbon; D001120:Arginine; D011392:Proline