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TPR files used for generating the data for analysis of"Maturation of the SARS-CoV-2 virus is regulated by dimerization of its main protease" paper. The names of the ZIP archives with theTPR files referto the simulation systems description inSupplementary Table 1 of the paper. TPR files were generated withGROMACS2020.1simulation packageforatomisticmolecular dynamics simulations. The force field used is Amber ff14SB force-field for the protein and the salt ions,and TIP3P parameters for water.The rest of the description clarifying the details of the simulation runs is present in the methodology section of the accompanying manuscript.

It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of TRKB, a BDNF receptor promoting neuronal plasticity and antidepressant responses, has a cholesterol-interaction site that may mediate the synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants bind to this cholesterol-interaction motif, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Docking simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB cholesterol-interaction motif or cholesterol depletion impaired BDNF-mediated plasticity, as well as cellular and behavioral responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and the allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which proposes a framework for how molecular effects of antidepressants are translated into clinical mood recovery.

Despite the vast amount of experimental and theoretical studies on the binding affinity of cations - especially the biologically relevant Na(+) and Ca(2+) - for phospholipid bilayers, there is no consensus in the literature. Here we show that by interpreting changes in the choline headgroup order parameters according to the 'molecular electrometer' concept [Seelig et al., Biochemistry, 1987, 26, 7535], one can directly compare the ion binding affinities between simulations and experiments. Our findings strongly support the view that in contrast to Ca(2+) and other multivalent ions, Na(+) and other monovalent ions (except Li(+)) do not specifically bind to phosphatidylcholine lipid bilayers at sub-molar concentrations. However, the Na(+) binding affinity was overestimated by several molecular dynamics simulation models, resulting in artificially positively charged bilayers and exaggerated structural effects in the lipid headgroups. While qualitatively correct headgroup order parameter response was observed with Ca(2+) binding in all the tested models, no model had sufficient quantitative accuracy to interpret the Ca(2+):lipid stoichiometry or the induced atomistic resolution structural changes. All scientific contributions to this open collaboration work were made publicly, using nmrlipids.blogspot.fi as the main communication platform. acceptedVersion