TY  - JOUR
AU  - Do, Trang N.
AU  - Carloni, Paolo
AU  - Varani, Gabriele
AU  - Bussi, Giovanni
TI  - RNA/Peptide Binding Driven by Electrostatics—Insight from Bidirectional Pulling Simulations
JO  - Journal of chemical theory and computation
VL  - 9
IS  - 3
SN  - 1549-9626
CY  - Washington, DC
PB  - American Chemical Society (ACS)
M1  - FZJ-2015-03616
SP  - 1720 - 1730
PY  - 2013
AB  - RNA/protein interactions play crucial roles in controlling gene expression. They are becoming important targets for pharmaceutical applications. Due to RNA flexibility and to the strength of electrostatic interactions, standard docking methods are insufficient. We here present a computational method which allows studying the binding of RNA molecules and charged peptides with atomistic, explicit-solvent molecular dynamics. In our method, a suitable estimate of the electrostatic interaction is used as an order parameter (collective variable) which is then accelerated using bidirectional pulling simulations. Since the electrostatic interaction is only used to enhance the sampling, the approximations used to compute it do not affect the final accuracy. The method is employed to characterize the binding of TAR RNA from HIV-1 and a small cyclic peptide. Our simulation protocol allows blindly predicting the binding pocket and pose as well as the binding affinity. The method is general and could be applied to study other electrostatics-driven binding events.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000316168700042
DO  - DOI:10.1021/ct3009914
UR  - https://juser.fz-juelich.de/record/201311
ER  -