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@ARTICLE{Raghavan:1009524,
author = {Raghavan, Bharath and Paulikat, Mirko and Ahmad, Katya and
Callea, Lara and Rizzi, Andrea and Ippoliti, Emiliano and
Mandelli, Davide and Bonati, Laura and De Vivo, Marco and
Carloni, Paolo},
title = {{D}rug {D}esign in the {E}xascale {E}ra: {A} {P}erspective
from {M}assively {P}arallel {QM}/{MM} {S}imulations},
journal = {Journal of chemical information and modeling},
volume = {63},
number = {12},
issn = {0095-2338},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2023-02854},
pages = {3647 - 3658},
year = {2023},
note = {Grant name: DBA01838 Innovative high-performance computing
applied to neurodegenerative diseasesOpen access
publication},
abstract = {The initial phases of drug discovery – in silico drug
design – could benefit from first principle Quantum
Mechanics/Molecular Mechanics (QM/MM) molecular dynamics
(MD) simulations in explicit solvent, yet many applications
are currently limited by the short time scales that this
approach can cover. Developing scalable first principle
QM/MM MD interfaces fully exploiting current exascale
machines – so far an unmet and crucial goal – will help
overcome this problem, opening the way to the study of the
thermodynamics and kinetics of ligand binding to protein
with first principle accuracy. Here, taking two relevant
case studies involving the interactions of ligands with
rather large enzymes, we showcase the use of our recently
developed massively scalable Multiscale Modeling in
Computational Chemistry (MiMiC) QM/MM framework (currently
using DFT to describe the QM region) to investigate
reactions and ligand binding in enzymes of pharmacological
relevance. We also demonstrate for the first time strong
scaling of MiMiC-QM/MM MD simulations with parallel
efficiency of $∼70\%$ up to >80,000 cores. Thus, among
many others, the MiMiC interface represents a promising
candidate toward exascale applications by combining machine
learning with statistical mechanics based algorithms
tailored for exascale supercomputers.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {37319347},
UT = {WOS:001020993900001},
doi = {10.1021/acs.jcim.3c00557},
url = {https://juser.fz-juelich.de/record/1009524},
}