TY  - JOUR
AU  - Raghavan, Bharath
AU  - Paulikat, Mirko
AU  - Ahmad, Katya
AU  - Callea, Lara
AU  - Rizzi, Andrea
AU  - Ippoliti, Emiliano
AU  - Mandelli, Davide
AU  - Bonati, Laura
AU  - De Vivo, Marco
AU  - Carloni, Paolo
TI  - Drug Design in the Exascale Era: A Perspective from Massively Parallel QM/MM Simulations
JO  - Journal of chemical information and modeling
VL  - 63
IS  - 12
SN  - 0095-2338
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2023-02854
SP  - 3647 - 3658
PY  - 2023
N1  - Grant name: DBA01838 Innovative high-performance computing applied to neurodegenerative diseasesOpen access publication
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 37319347
UR  - <Go to ISI:>//WOS:001020993900001
DO  - DOI:10.1021/acs.jcim.3c00557
UR  - https://juser.fz-juelich.de/record/1009524
ER  -