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@ARTICLE{Rossetti:201098,
author = {Rossetti, Giulia},
title = {{L}igand {B}inding on {I}ntrinsic {D}isordered {P}roteins:
{F}ocus on {H}uman {A}lpha-{S}ynuclein},
journal = {Biophysical journal},
volume = {104},
number = {2},
issn = {0006-3495},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {FZJ-2015-03403},
pages = {379a},
year = {2013},
abstract = {Intrinsically disordered proteins (IDPs) are involved in a
wide variety of human diseases (1). Hence, interfering with
the function of IDP-disease-associated proteins offers a
highly attractive objective for drug development (2).
Unfortunately, rational approaches have been hampered so far
because of variety of problems absent in traditional drug
design protocols. These issues include the highly dynamic
nature of IDPs (3), the presence of local and long-range
conformational rearrangements (4), transient secondary
structure, transient long-range tertiary structure (5,
6).Here we present a combined NMR/molecular dynamics
protocol that provides quantitative information on ligand
poses to IDPs. The approach is based on a geometrical-based
analysis of MD trajectory with a flexibility index able to
detect conformational transition of residues' backbone
(Caliandro, C, Rossetti, G, Carloni, P, 2012 JCTC in press).
The protocol is applied on dopamine in complex with the
naturally unfolded protein human α-synuclein. The proposed
protocol is very general and it could be used to investigate
the pose of novel molecules binding to any IDP.},
cin = {JSC / IAS-5},
ddc = {570},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)IAS-5-20120330},
pnm = {411 - Computational Science and Mathematical Methods
(POF2-411)},
pid = {G:(DE-HGF)POF2-411},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000316074303437},
doi = {10.1016/j.bpj.2012.11.2111},
url = {https://juser.fz-juelich.de/record/201098},
}