Best Practices in Constant pH MD Simulations: Accuracy and Sampling
Various approaches have been proposed to include the effect of pH in molecular dynamics (MD) simulations. Among these, the λ-dynamics approach proposed by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414−2423] can be performed with little computational overhead and hfor each typeence be used to routinely perform MD simulations at microsecond time scales, as shown in the accompanying paper [Aho, N. et al. J. Chem. Theory Comput.2022, DOI: 10.1021/acs.jctc.2c00516]. At such time scales, however, the accuracy of the molecular mechanics force field and the parametrization becomes critical. Here, we address these issues and provide the community with guidelines on…
Scalable Constant pH Molecular Dynamics in GROMACS
Molecular dynamics (MD) computer simulations are used routinely to compute atomistic trajectories of complex systems. Systems are simulated in various ensembles, depending on the experimental conditions one aims to mimic. While constant energy, temperature, volume, and pressure are rather straightforward to model, pH, which is an equally important parameter in experiments, is more difficult to account for in simulations. Although a constant pH algorithm based on the λ-dynamics approach by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys.1996, 105, 2414–2423] was implemented in a fork of the GROMACS molecular dynamics program, uptake has been rather limited, presumably due to…
Inverse Conformational Selection in Lipid–Protein Binding
International audience; Interest in lipid interactions with proteins and other biomolecules is emerging not only in fundamental biochemistry but also in the field of nanobiotechnology where lipids are commonly used, for example, in carriers of mRNA vaccines. The outward-facing components of cellular membranes and lipid nanoparticles, the lipid headgroups, regulate membrane interactions with approaching substances, such as proteins, drugs, RNA, or viruses. Because lipid headgroup conformational ensembles have not been experimentally determined in physiologically relevant conditions, an essential question about their interactions with other biomolecules remains unanswered: Do headgroups excha…
Assembly of Spinach Chloroplast ATP Synthase Rotor Ring Protein-Lipid Complex
Rotor ATPases are large multisubunit membrane protein complexes found in all kingdoms of life. The membrane parts of these ATPases include a ring-like assembly, so-called c-ring, consisting of several subunits c, plugged by a patch of phospholipids. In this report, we use a nature-inspired approach to model the assembly of the spinach (Spinacia oleracea) c14 ring protein-lipid complex, where partially assembled oligomers are pulled toward each other using a biasing potential. The resulting assemblies contain 23 to 26 encapsulated plug lipids, general position of which corresponds well to experimental maps. However, best fit to experimental data is achieved with 15 to 17 lipids inside the c-…