The time step of atomistic molecular dynamics (MD) simulations is determined by the fastest motions in the system and is typically limited to 2 fs. An increasingly popular approach is to increase the mass of the hydrogen atoms to ∼3 amu and decrease the mass of the parent atom by an equivalent amount. This approach, known as hydrogen-mass repartitioning (HMR), permits time steps up to 4 fs with reasonable simulation stability. While HMR has been applied in many published studies to date, it has not been extensively tested for membrane-containing systems. Here, we compare the results of simulations of a variety of membranes and membrane–protein systems run using a 2 fs time step and a 4 fs time step with HMR. For pure membrane systems, we find almost no difference in structural properties, such as area-per-lipid, electron density profiles, and order parameters, although there are differences in kinetic properties such as the diffusion constant. Conductance through a porin in an applied field, partitioning of a small peptide, hydrogen-bond dynamics, and membrane mixing show very little dependence on HMR and the time step. We also tested a 9 Å cutoff as compared to the standard CHARMM cutoff of 12 Å, finding significant deviations in many properties tested. We conclude that HMR is a valid approach for membrane systems, but a 9 Å cutoff is not.

Accelerated molecular dynamics (aMD) is an enhanced sampling technique that expedites conformational space sampling by reducing the barriers separating various low-energy states of a system. Here, we present the first application of the aMD method on lipid membranes. Altogether, ∼1.5 μs simulations were performed on three systems: a pure POPC bilayer, a pure DMPC bilayer, and a mixed POPC:DMPC bilayer. Overall, the aMD simulations are found to produce significant speedup in trans–gauche isomerization and lipid lateral diffusion versus those in conventional MD (cMD) simulations. Further comparison of a 70-ns aMD run and a 300-ns cMD run of the mixed POPC:DMPC bilayer shows that the two simulations yield similar lipid mixing behaviors, with aMD generating a 2–3-fold speedup compared to cMD. Our results demonstrate that the aMD method is an efficient approach for the study of bilayer structural and dynamic properties. On the basis of simulations of the three bilayer systems, we also discuss the impact of aMD parameters on various lipid properties, which can be used as a guideline for future aMD simulations of membrane systems.

The ‘Mystery Interval’ (MI, 17.5−14.5 ka) was the first stage of the last deglaciation, a key interval for understanding mechanisms of glacial–interglacial cycles. To elucidate possible causes of the MI, here we present three high-resolution, precisely dated oxygen-isotope records of stalagmites from Qingtian and Hulu Caves in China, reflecting changes in the East Asian summer monsoon (EASM) then. Based on well-established chronologies using precise 230Th dates and annual-band counting results, the two-cave δ18O profiles of ~7-yr resolution match well at decadal timescales. Both of the two-cave records document an abrupt weakening (2‰ of δ18O rise within 20 yr) in the EASM at ~16.1 ka, coinciding with the transition of the two-phased MI reconstructed from New Mexico's Lake Estancia. Our results indicate that the maximum southward displacement of the Intertropical Convergence Zone and associated southward shift of polar jet stream may generate this two-phase feature of the MI during that time. We also discover a linear relationship among decreasing EASM intensity, rising atmospheric CO2 and weakening Atlantic Meridional Overturning Circulation between the MI and Younger Dryas episodes, suggesting a strong coupling of atmospheric/oceanic circulations in response to the millennial-scale forcing, which in turn regulates global climate changes and carbon cycles.