Genarris: Random generation of molecular crystal structures and fast screening with a Harris approximation.

We present Genarris, a Python package that performs configuration space screening for molecular crystals of rigid molecules by random sampling with physical constraints. For fast energy evaluations, Genarris employs a Harris approximation, whereby the total density of a molecular crystal is constructed via superposition of single molecule densities. Dispersion-inclusive density functional theory is then used for the Harris density without performing a self-consistency cycle. Genarris uses machine learning for clustering, based on a relative coordinate descriptor developed specifically for molecular crystals, which is shown to be robust in identifying packing motif similarity. In addition to random structure generation, Genarris offers three workflows based on different sequences of successive clustering and selection steps: the "Rigorous" workflow is an exhaustive exploration of the potential energy landscape, the "Energy" workflow produces a set of low energy structures, and the "Diverse" workflow produces a maximally diverse set of structures. The latter is recommended for generating initial populations for genetic algorithms. Here, the implementation of Genarris is reported and its application is demonstrated for three test cases.

Cation-dependent segregation phenomena and phase behavior in model membrane systems containing phosphatidylserine: influence of cholesterol and acyl chain composition.

The addition of Ca2+ to model membrane systems containing phosphatidylserine (PS) can have remarkable effects on the distribution of PS and the overall polymorphic phase [bilayer or hexagonal (HII)] assumed by the lipid mixture. In this study, we examine the influence of Ca2+ on lipid mixtures composed of well-defined (synthetic) species of PS, phosphatidylethanolamine (PE), and phosphatidylcholine (PC) in the presence and absence of cholesterol by employing 31P and 2H NMR, freeze-fracture, and X-ray techniques. It is shown that whereas Ca2+ can segregate PS into crystalline cochleate domains in equimolar mixtures of dioleoyl-PE and dioleoyl-PS (DOPS), such effects are not observed for mixtures containing more unsaturated (dilinoleoyl) species of PS. The addition of cholesterol to these PE-PS systems inhibits Ca2+-induced segregation of DOPS and facilitates Ca2+-triggered hexagonal (HII) phase formation for both the PE and the PS components. In contrast, in equimolar mixtures of DOPS with dioleoyl-PC, Ca2+-induced segregation of phospholipid is not affected by the presence of up to 33 mol % cholesterol. These and related effects suggest that, in multicomponent biomembrane systems containing both PE and cholesterol, phase segregation of PS by Ca2+ may not be readily achievable. These results are discussed with regard to the reliability of 31P NMR phase identifications of phospholipid structure in model and biological membranes and demonstrate that in mixed lipid systems the influence of divalent cations on lipid distribution and structure can be exquisitely sensitive to details of the local lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphic phase preferences of phosphatidic acid: A 31P and 2H NMR study.

31P NMR, 2H NMR and freeze fracture techniques have been employed to investigate the structural preferences of dioleoyl phosphatidic acid (DOPA) under various conditions of pH and divalent cation content. It is shown that DOPA increasingly prefers the HII organization below pH 5, and that low levels of Ca2+ and Mg2+ (Me2+/DOPA = 0.5) induce HII phase structure for pH less than 6.0. Higher Mg2+ and Ca2+ levels (Me2+/DOPA greater than 1.0) induce more complex structures at pH greater than 5.0 which may correspond to intermediates between lamellar and HII organization. This work illustrates the utility of 2H NMR techniques in conjunction with suitable 2H labelled lipids to provide structural information on lipid-water systems, and suggests that 31P NMR techniques for determinations of lipid organization can be applied to advantage in PA containing membranes.

Influence of cholesterol on the structural preferences of dioleoylphosphatidylethanolamine-dioleoylphosphatidylcholine systems: a phosphorus-31 and deuterium nuclear magnetic resonance study.

The polymorphic phase behavior of mixtures of synthetic dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) and the influence of cholesterol on these phase preferences have been investigated by employing nuclear magnetic resonance (NMR) techniques. In particular, 31P NMR procedures are utilized to study the overall phase preferences of these mixed systems, whereas 2H NMR is employed to monitor the structural preferences of individual components of these systems by using versions of DOPE and DOPC which are deuterium (2H) labeled at the C11 position of the acyl chains. The results obtained show that DOPE-DOPC systems containing as little as 20 mol % DOPC initially assume lamellar structure at 40 degrees C, even though DOPE in isolation prefers the hexagonal (HII) organization at this temperature. However, this lamellar organization appears to represent a metastable state, as incubation for extended periods at 40 degrees C results in formation of a structure, possibly the cubic phase, in which the phospholipids experience isotropic motional averaging. The addition of cholesterol induces hexagonal (HII) phase organization. 2H NMR studies of appropriately labeled versions of these systems indicate that cholesterol does not produce such effects by associating preferentially with either DOPE or DOPC. Further, in situations where bilayer, hexagonal, or "isotropic" phases coexist in the same sample, the phospholipids exhibit apparently ideal mixing behavior.

Lipid requirements for the aggregation of CTP:phosphocholine cytidylyltransferase in rat liver cytosol.

Two forms of CTP:phosphocholine cytidylyltransferase were identified in rat liver cytosol by gel filtration chromatography. The low molecular weight form (L form) is the major form in fresh cytosol. The enzyme associates into a high molecular weight form (H form) upon storage of the cytosol at 4 degrees C. Aggregation of the purified L form of cytidylyltransferase is caused by total rat liver lipids, neutral lipids, diacylglycerol, or phosphatidylglycerol. Diacylglycerol was the only lipid isolated from the rat liver that caused aggregation of the purified enzyme. Although the addition of diacylglycerol to the cytosol did not change the amount of aggregation of the enzyme, a 2.5-fold increase in H form was observed in cytosol pretreated with phospholipase C, or in cytosol from rats fed a high cholesterol diet. In both of these cytosolic preparations, the concentration of diacylglycerol was elevated twofold. Phosphatidylglycerol did not seem to affect the association of the enzyme in cytosol since it is present in very low concentrations in the rat liver cytosol, and its degradation in cytosol by a specific phospholipase did not affect the rate of aggregation. The results suggest that diacylglycerol in an appropriate form is required for association of cytidylyltransferase in rat liver cytosol.