Lipid adhesion forces can be measured using several experimental techniques, but none of these techniques provide insight on the atomic level. Therefore, we performed extensive nonequilibrium molecular dynamics simulations of a phospholipid membrane in the liquid-crystalline phase out of which individual lipid molecules were pulled. In our method, as an idealization of the experimental setups, we have simply attached a harmonic spring to one of the lipid headgroup atoms. Upon retraction of the spring, the force needed to drag the lipid out of the membrane is recorded. By simulating different retraction rates, we were able to investigate the high pull rate part of the dynamical spectrum of lipid adhesion forces. We find that the adhesion force increases along the unbinding path, until the point of rupture is reached. The maximum value of the adhesion force, the rupture force, decreases as the pull rate becomes slower, and eventually enters a friction-dominated regime. The computed bond lengths depend on the rate of rupture, and show some scatter due to the nonequilibrium nature of the experiment. On average, the bond length increases from approximately 1.7 nm to 2.3 nm as the rates go down. Conformational analyses elucidate the detailed mechanism of lipid-membrane bond rupture. We present results of over 15 ns of membrane simulations. Implications for the interpretation and understanding of experimental rupture data are discussed.

The ESCRT pathway mediates a series of important cellular membrane remodeling and fission events, including cytokinetic abscission. During these processes, ESCRT-III family proteins, including CHMP1B and IST1, form filaments that appear to constrict membranes and facilitate fission. Here, we report the first structure of ''open'' and assembled ESCRT-III proteins. Nearatomic resolution electron cryomicroscopy reveals that filaments comprise a copolymeric assembly of an open conformation inner strand and, unexpectedly, a closed conformation outer strand.

Bioenergetic membranes are the key cellular structures responsible for coupled energy-conversion processes, which supply ATP and important metabolites to the cell. Here, we report the first 100million atom-scale model of an entire photosynthetic organelle, a chromatophore membrane vesicle from a purple bacterium, which reveals the rate-determining steps of membrane-mediated energy conversion. Molecular dynamics simulations of this bioenergetic organelle elucidate how the network of bioenergetic proteins influences membrane curvature and demonstrates the impact of thermal disorder on photosynthetic excitation transfer. Brownian dynamics simulations of the quinone and cytochrome c2 charge carriers within the chromatophore interior probe the mechanisms of nanoscale charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a rate-kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore's structural integrity and robust energy conversion. Put together, the hybrid structure determination and systems-level modeling of the chromatophore, in conjunction with optical spectroscopy, illuminate the chemical and organizational design principles of biological membranes that foster energy storage and transduction in living cells. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights on the mechanism of cellular aging are inferred. This endeavor made feasible through the advent of petascale supercomputers, paves the way to first-principles modeling of whole living cells.

Atomistic and coarse-grained simulations can be a great help in uncovering the mechanisms of physical processes at microscopic and mesoscopic levels at time scales ranging from femtoseconds to milliseconds. Any simulation study involves (1) setting up an appropriate simulation system representing the physical problem, (2) running the simulation and collecting information about the system, and (3) analyzing the collected data. The last step eventually leads to final conclusions about the system. Software for molecular simulation has been in development for many years and a number of high quality freely distributed general purpose simulation packages is available for researchers. Data analysis tools are usually less general as they often depend on a specific research project and the system under investigation. While many simulation packages come with a set of some general data analysis utilities, it is not unusual for such analysis tools to be developed on a per project basis inside research groups. Interestingly, there is a very limited set of available tools for setting up simulation systems, even though this is the very first and vital step of every simulation study. This lack of convenient general simulation system generators sometimes may even dictate the kind of simulations done based on the available initial systems rather than on the system being the best for a particular problem. In this work we describe a general software tool, bio.b-gen, for the creation of initial systems for biological molecular simulations. A number of case systems are demonstrated using an atomistic force field as well as the coarse grained MARTINI force field. The tool is designed to generate initial systems for the GROMACS general simulation package.

CL variants. This work revealed that MLCL, which lacks a lipid tail, does not allow for the hydrophobic interactions and unfolding of cytochrome c, a requisite step in promoting peroxidase activity and of the apoptotic program. Finally, we use a combination of electrokinetic measurements and fluorescence-based approaches to address the ionization properties of the phosphate esters among CL variants. In contrast to the dominant paradigm in which a resonance-stabilized bicyclic headgroup structure promotes two disparate pKa values, we find the CL head group behaves as a strong dibasic acid, and exists as a dianion at physiological pH. Moreover, the ionization properties of the CL head group are similar for all variants examined.