Expanding the boundaries of ligand–target modeling by exascale calculations

Abstract

Molecular simulations and molecular docking are widely used tools to investigate ligand/target interactions and in drug design. High‐performance computing (HPC) is boosting both the accuracy and predictive power of these approaches. With the advent of exascale computing, HPC may become standardly applied in many drug design campaigns and pharmacological applications. This review discusses how innovative HPC algorithms and hardware are being exploited in current simulations and docking codes, pointing also at some of the limitations of these approaches. The focus is on technical aspects which might not be all that familiar to the computational pharmacologist. This article is categorized under: Software > Molecular Modeling Software > Simulation Methods Structure and Mechanism > Computational Biochemistry and Biophysics

Proton Transfers to DNA in Native Electrospray Ionization Mass Spectrometry: A Quantum Mechanics/Molecular Mechanics Study

“…The classical MD simulations and the MM calculations in the QM/MM calculations were performed using the GROMACS program package . The QM calculations were performed either by CP2K (for II , using the API QM/MM interface of GROMACS) or by CPMD (for I , using the MiMiC QM/MM interface). − The PLUMED plugin was used to introduce the biases in the umbrella sampling QM/MM simulations. , …”

“… 29 The QM calculations were performed either by CP2K 46 (for II , using the API QM/MM interface of GROMACS) or by CPMD 53 (for I , using the MiMiC QM/MM interface). 54 − 56 The PLUMED plugin was used to introduce the biases in the umbrella sampling QM/MM simulations. 57 , 58 …”

Proton Transfers to DNA in Native Electrospray Ionization Mass Spectrometry: A QM/MM Study

“…28 The QM calculations were performed either by CP2K 45 (for II , using the API QM/MM interface of GROMACS) or by CPMD 52 (for I , using the MiMiC QM/MM interface). 53–55 The PLUMED plugin was used to introduce the biases in the umbrella sampling QM/MM simulations. 56,57…”

Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective

“…7 Exascale calculations however remain one of the major challenges in molecular simulations ( Hospital et al, 2015 ; Páll et al, 2015 ). Recent advances in massively scalable QM/MM codes, such as that developed in Juelich in collaboration with European universities ( Olsen et al, 2019 ; Bolnykh et al, 2020a ) (see Supplementary Material S7 ) and their successful applications to predict free energy landscapes associated with biological processes ( Bolnykh et al, 2020a ; Chiariello et al, 2020 ) brings us to suggest that in a not-too-far future QM/MM calculations may exploit the unprecedented power of exascale computing for direct MD simulations of ligand (un)binding ( Bolnykh et al, 2020b , Bolnykh et al, 2021 ).…”