Atomistic Model for Nearly Quantitative Simulations of Langmuir Monolayers

Lung surfactant and a tear film lipid layer are examples of biologically relevant macromolecular structures found at the air–water interface. Because of their complexity, they are often studied in terms of simplified lipid layers, the simplest example being a Langmuir monolayer. Given the profound biological significance of these lipid assemblies, there is a need to understand their structure and dynamics on the nanoscale, yet there are not many techniques able to provide this information. Atomistic molecular dynamics simulations would be a tool fit for this purpose; however, the simulation models suggested until now have been qualitative instead of quantitative. This limitation has mainly stemmed from the challenge to correctly describe the surface tension of water with simulation parameters compatible with other biomolecules. In this work, we show that this limitation can be overcome by using the recently introduced four-point OPC water model, whose surface tension for water is demonstrated to be quantitatively consistent with experimental data and which is also shown to be compatible with the commonly employed lipid models. We further establish that the approach of combining the OPC four-point water model with the CHARMM36 lipid force field provides nearly quantitative agreement with experiments for the surface pressure–area isotherm for POPC and DPPC monolayers, also including the experimentally observed phase coexistence in a DPPC monolayer. The simulation models reported in this work pave the way for nearly quantitative atomistic studies of lipid-rich biological structures at air–water interfaces

Calcium Sensing by Recoverin: Effect of Protein Conformation on Ion Affinity

The detailed functional mechanism of recoverin, which acts as a myristoyl switch at the rod outer-segment disk membrane, is elucidated by direct and replica-exchange molecular dynamics. In accord with NMR structural evidence and calcium binding assays, simulations point to the key role of enhanced calcium binding to the EF3 loop of the semiopen state of recoverin as compared to the closed state. This 2–4-order decrease in calcium dissociation constant stabilizes the semiopen state in response to the increase of cytosolic calcium concentration in the vicinity of recoverin. A second calcium ion then binds to the EF2 loop and, consequently, the structure of the protein changes from the semiopen to the open state. The latter has the myristoyl chain extruded to the cytosol, ready to act as a membrane anchor of recoverin

nmrlipids.blogspot.fi — on October 25th 2015

<p>Snapshot of the blog nmrlipids.blogspot.fi on October 25th 2015.</p> <p> </p> <p>The NMRlipids project is an open scientific collaboration to understand the atomistic resolution structures of lipid bilayers through classical molecular dynamics simulations. The project is progressed through the comments in the blog and using the GitHub organization (see links). The main results are also published in traditional peer reviewed scientific journals.</p