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@ARTICLE{Capelli:866016,
author = {Capelli, Riccardo and Carloni, Paolo and Parrinello,
Michele},
title = {{E}xhaustive {S}earch of {L}igand {B}inding {P}athways via
{V}olume-{B}ased {M}etadynamics},
journal = {The journal of physical chemistry letters},
volume = {10},
number = {12},
issn = {1948-7185},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2019-05276},
pages = {3495 - 3499},
year = {2019},
abstract = {Determining the complete set of ligands’
binding–unbinding pathways is important for drug discovery
and for rational interpretation of mutation data. Here we
have developed a metadynamics-based technique that addresses
this issue and allows estimating affinities in the presence
of multiple escape pathways. Our approach is shown on a
lysozyme T4 variant in complex with a benzene molecule. The
calculated binding free energy is in agreement with
experimental data. Remarkably, not only were we able to find
all the previously identified ligand binding pathways, but
also we identified three pathways previously not identified
as such. These results were obtained at a small
computational cost, making this approach valuable for
practical applications, such as screening of small compound
libraries.},
cin = {IAS-5 / JARA-HPC / INM-9},
ddc = {530},
cid = {I:(DE-Juel1)IAS-5-20120330 / $I:(DE-82)080012_20140620$ /
I:(DE-Juel1)INM-9-20140121},
pnm = {574 - Theory, modelling and simulation (POF3-574) / HBP
SGA2 - Human Brain Project Specific Grant Agreement 2
(785907) / HPC-aided design of drugs with improved kinetics
of binding $(jias5d_20181101)$},
pid = {G:(DE-HGF)POF3-574 / G:(EU-Grant)785907 /
$G:(DE-Juel1)jias5d_20181101$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31188006},
UT = {WOS:000472804700048},
doi = {10.1021/acs.jpclett.9b01183},
url = {https://juser.fz-juelich.de/record/866016},
}