Modeling Structural Heterogeneity in Proteins From X-Ray Data

Abstract: In a crystallographic experiment, a protein is precipitated to obtain a crystalline sample (crystal) containing many copies of the molecule. An electron density map (edm) is calculated from diffraction images obtained from focusing X-rays through the sample at different angles. This involves iterative phase determination and density calculation. The protein conformation is modeled by placing the atoms in 3-D space to best match the electron density. In practice, the copies of a protein in a crystal are not exactly in the same conformation. Consequently the obtained edm, which corresponds to the cumulative distribution of atomic positions over all conformations, is blurred. Existing modeling methods compute an “average ” protein conformation by maximizing its fit with the edm and explain structural heterogeneity in the crystal with a harmonic distribution of the position of each atom. However, proteins undergo coordinated conformational variations leading to substantial correlated changes in atomic positions. These variations are biologically important. This paper presents a sample-select approach to model structural heterogeneity by computing an ensemble of conformations (along with occupancies) that, collectively, provide a near-optimal explanation of the edm. The focus is on deformable protein fragments, mainly loops and side-chains. Tests were successfully conducted on simulated and experimental edms.

Generalist predators in organically and conventionally managed grass-clover fields: implications for conservation biological control

Organically managed agroecosystems rely in part on biological control to prevent pest outbreaks. Generalist predators (Araneae, Carabidae and Staphylinidae) are a major component of the natural enemy community in agroecosystems. We assessed the seasonal dynamics of major generalist predator groups in conventionally and organically managed grass–clover fields that primarily differed by fertilisation strategy. We further established an experiment, manipulating the abundant wolf spider genus Pardosa, to identify the importance of these predators for herbivore suppression in the same system and growth period. Organic management significantly enhanced ground-active spider numbers early and late in the growing season, with potentially positive effects of plant cover and non-pest decomposer prey. However, enhancing spider numbers in the field experiment did not improve biological control in organically managed grass–clover fields. Similar to the survey results, reduced densities of Pardosa had no short-term effect on any prey taxa; however, spider guild structure changed in response to Pardosa manipulation. In the presence of fewer Pardosa, other ground-running spiders were more abundant;therefore, their impact on herbivore numbers may have been elevated, possibly cancelling increases in herbivore numbers because of reduced predation by Pardosa. Our results indicate positive effects of organic farming on spider activity density; however, our survey data and the predator manipulation experiment failed to find evidence that ground-running spiders reduced herbivore numbers. We therefore suggest that a positive impact of organic fertilisers on wolf spiders in grass–clover agroecosystems may not necessarily improve biological control when compared with conventional farming