jp312423y_si_001.pdf (161.95 kB)
Binding Preference of Carbon Nanotube Over Proline-Rich Motif Ligand on SH3-Domain: A Comparison with Different Force Fields
journal contribution
posted on 2013-04-04, 00:00 authored by Biyun Shi, Guanghong Zuo, Peng Xiu, Ruhong ZhouWith
the widespread applications of nanomaterials such as carbon
nanotubes, there is a growing concern on the biosafety of these engineered
nanoparticles, in particular their interactions with proteins. In
molecular simulations of nanoparticle–protein interactions,
the choice of empirical parameters (force fields) plays a decisive
role, and thus is of great importance and should be examined carefully
before wider applications. Here we compare three commonly used force
fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding
of a single wall carbon nanotube (SWCNT) with a native proline-rich
motif (PRM) ligand on its target protein SH3 domain, a ubiquitous
protein–protein interaction mediator involved in signaling
and regulatory pathways. We find that the SWCNT displays a general
preference over the PRM in binding with SH3 domain in all the three
force fields examined, although the degree of preference can be somewhat
different, with the AMBER force field showing the highest preference.
The SWCNT prevents the ligand from reaching its native binding pocket
by (i) occupying the binding pocket directly, and (ii) binding with
the ligand itself and then being trapped together onto some off-sites.
The π–π stacking interactions between the SWCNT
and aromatic residues are found to play a significant role in its
binding to the SH3 domain in all the three force fields. Further analyses
show that even the SWCNT-ligand binding can also be relatively more
stable than the native ligand-protein binding, indicating a serious
potential disruption to the protein SH3 function.