Integrating cellular and molecular structures and dynamics into whole-cell models

Thirty years of molecular dynamics simulations on posttranslational modifications of proteins

“…Offering probability distributions relative to the specific activity of a protein after PTM installation could drastically improve the accuracy of systems-scale kinetic analyses for multiscale modeling endeavors. 1,[282][283][284] State-of-the-art structure predictions and faster computing hardware now unleash an array of in silico opportunities to realistically characterize PTMs for proteins that lack experimentally resolved structures or are simply understudied. 285 Together, modern MD simulations can join theory and experiments in informing us as to how the structuredynamic perturbations caused by PTMs impact whole-cell physiology.…”

“…285 Together, modern MD simulations can join theory and experiments in informing us as to how the structuredynamic perturbations caused by PTMs impact whole-cell physiology. 283,284 Despite the opportunities they provide in characterizing PTMs, it is worth recognizing the caveats of molecular simulations. A major caveat to molecular simulations is that the process of covalent bond breakage and formation is extremely expensive to model.…”

“…285 Together, modern MD simulations can join theory and experiments in informing us as to how the structure-dynamic perturbations caused by PTMs impact whole-cell physiology. 283,284…”

Monte Carlo and Molecular Dynamics Simulations to Explain Biomembrane Meso-Patterning by a Composition-Curvature Coupling Mechanism

“…In the era of exascale computing 92,93 , it is tempting to design molecular systems to study from organelles 8,94 to viruses 94,95 or even an entire cell [96][97][98] . Yet, the computing power necessary to simulate such large systems is still very huge and prevents one from reaching simulated timescales useful to decipher even simple phenomena such as diffusion of large molecules 94 without even mentioning relevant biological time scales of milliseconds or longer.…”

Molecular dynamics simulation of an entire cell

“…State-of-the-art simulations, containing hundreds of millions of atoms, include dynamic models of a photosynthetic chromatophore vesicle ( Singharoy et al, 2019 ), the nuclear core complex ( Mosalaganti et al, 2022 ), the membranes of a mitochondrion ( Pezeshkian et al, 2020 ), the bacterial cytoplasm ( Yu et al, 2016 ), and a virus particle embedded in a nanoscale aerosol droplet ( Dommer et al, 2022 ). The natural next step is, arguably, the scale of entire cells ( Bhat and Balaji, 2020 ; Khalid and Rouse, 2020 ; Luthey-Schulten et al, 2022 ; Thornburg et al, 2022 ).…”