How do potentials derived from structural databases relate to “true” potentials?

Knowledge-based potentials are used widely in protein folding and inverse folding algorithms. Two kinds of derivation methods are used. (1) The interactions in a database of known protein structures are assumed to obey a Boltzmann distribution. (2) The stability of the native folds relative to a manifold of misfolded structures is optimized. Here, a set of previously derived contact and secondary structure propensity potentials, taken as the "true" potentials, are employed to construct an artificial protein structural database from protein fragments. Then, new sets of potentials are derived to see how they are related to the true potentials. Using the Boltzmann distribution method, when the stability of the structures in the database lies within a certain range, both contact potentials and secondary structure propensities can be derived separately with remarkable accuracy. In general, the optimization method was found to be less accurate due to errors in the "excess energy" contribution. When the excess energy terms are kept as a constraint, the true potentials are recovered exactly.     

A comparative analysis of the equilibrium dynamics of a designed protein inferred from NMR,X‐ray,and computations

A detailed analysis of high‐resolution structural data and computationally predicted dynamics was carried out for a designed sugar‐binding protein. The mean‐square deviations in the positions of residues derived from nuclear magnetic resonance (NMR) models and those inferred from X‐ray crystallographic B‐factors for two different crystal forms were compared with the predictions based on the Gaussian Network Model (GNM) and the results from molecular dynamics (MD) simulations. GNM systematically yielded a higher correlation than MD, with experimental data, suggesting that the lack of atomistic details in the coarse‐grained GNM is more than compensated for by the mathematically exact evaluation of fluctuations using the native contacts topology. Evidence is provided that particular loop motions are curtailed by intermolecular contacts in the crystal environment causing a discrepancy between theory and experiments. Interestingly, the information conveyed by X‐ray crystallography becomes more consistent with NMR models and computational predictions when ensembles of X‐ray models are considered. Less precise (broadly distributed) ensembles indeed appear to describe the accessible conformational space under native state conditions better than B‐factors. Our results highlight the importance of using multiple conformations obtained by alternative experimental methods, and analyzing results from both coarse‐grained models and atomic simulations, for accurate assessment of motions accessible to proteins under native state conditions. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

织物电极的皮肤-电极接触阻抗测量方法分析

随着可穿戴式健康监测技术的发展,新型心电传感器-织物电极成为人们关注的热点,本文对织物电极的皮肤-电极接触阻抗测量方法进行了综述。首先介绍了织物电极的概念,分析了织物电极的皮肤-电极电化学界面、皮肤-电极电化学界面的等效电路和简化电路模型,得出了皮肤-电极接触阻抗的计算公式;其次,将皮肤-电极接触阻抗的测量方法归纳为直接测量法、参比测量法和模拟皮肤测量法三类,讨论了它们的测量原理和优缺点。本文认为需将模拟皮肤测量法和真实皮肤测量法有机结合,才能有效评价织物电极的阻抗特性,为织物电极的性能评价和心电信号采集电路的设计提供重要依据。最后,本文对织物电极待解决的问题进行了分析讨论。     

Information‐theoretic analysis of the reference state in contact potentials used for protein structure prediction

Using information‐theoretic concepts, we examine the role of the reference state, a crucial component of empirical potential functions, in protein fold recognition. We derive an information‐based connection between the probability distribution functions of the reference state and those that characterize the decoy set used in threading. In examining commonly used contact reference states, we find that the quasi‐chemical approximation is informatically superior to other variant models designed to include characteristics of real protein chains, such as finite length and variable amino acid composition from protein to protein. We observe that in these variant models, the total divergence, the operative function that quantifies discrimination, decreases along with threading performance. We find that any amount of nativeness encoded in the reference state model does not significantly improve threading performance. A promising avenue for the development of better potentials is suggested by our information‐theoretic analysis of the action of contact potentials on individual protein sequences. Our results show that contact potentials perform better when the compositional properties of the data set used to derive the score function probabilities are similar to the properties of the sequence of interest. Results also suggest to use only sequences of similar composition in deriving contact potentials, to tailor the contact potential specifically for a test sequence. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

A Preliminary Study of the Surface Properties of Earthworms and Their Relations to Non-Stain Behaviour

The surface properties of earthworms were studied using nitrogen adsorption/desorption isotherm and dynamic contact angle measurement with the aim to understand their non-stain behaviour. The results obtained by applying dynamic contact angle technique using water, glycerol, cooking oil and dimethylsilicone show that the surface properties of earthworms are a function of time. The critical surface energy, calculated using advancing angle, is as low as 11 × 10~(-3) J·m~(-2). However this hydrophobic behaviour at the initial contact moment changes progressively into hydrophilic as time goes by. This behaviour together with the creeping movement of corrugated surface is believed to be responsible for the non-stain behaviour of earthworms. The nitrogen adsorption isotherm of dried skin of earthworms at 77.3 K exhibits more or less Type V isotherm with surface area of 13 m~2·g~(-1) calculated using the α_s plot. The Type V isotherm is the indication of weak interaction between nitrogen and the worm surface.     

Using differential introgression in hybrid zones to identify genomic regions involved in speciation

Hybrids between species provide information about the evolutionary processes involved in divergence. In addition to creating hybrids in the laboratory, biologists can take advantage of natural hybrid zones to understand the factors that shape gene flow between divergent lineages. In the early stages of speciation, most regions of the genome continue to flow freely between populations. Alternatively, the subset of the genome that confers reproductive barriers between nascent species is expected to reject introgression. Now enabled by advances in genomics, this perspective is motivating detailed comparisons of gene flow across genomic regions in hybrid zones. Here, I review methods for measuring and interpreting introgression at multiple loci in hybrid zones, focusing on the problem of identifying loci that contribute to reproductive isolation. Emerging patterns from multi-locus studies of hybrid zones are highlighted, including remarkable variance in introgression across the genome. Although existing methods have been useful, there is scope for development of new analytical approaches that better connect differential patterns of gene flow in hybrid zones with current knowledge of speciation mechanisms. I outline future prospects for differential introgression studies on a genomic scale.     

The supramolecular assemblies of voltage-dependent anion channels in the native membrane

Voltage-dependent anion channels (VDACs) are major constituents of the outer mitochondrial membrane (OMM). These primary transporters of nucleotides, ions and metabolites mediate a substantial portion of the OMM molecular traffic. To study the native supramolecular organization of the VDAC, we have isolated, characterized and imaged OMMs from potato tubers. SDS-PAGE and mass spectrometry of OMMs revealed the presence of the VDAC isoforms POM34 and POM36, as well as the translocase of the OMM complex. Tubular two-dimensional crystals of the VDAC spontaneously formed after incubation of OMMs for two to three months at 4 degrees C. Transmission electron microscopy revealed an oblique lattice and unit cells housing six circular depressions arranged in a hexagon. Atomic force microscopy of freshly isolated OMMs demonstrated (i) the existence of monomers to tetramers, hexamers and higher oligomers of the VDAC and (ii) its spatial arrangement within the oligomers in the native membrane. We discuss the importance of the observed oligomerization for modulation of the VDAC function, for the binding of hexokinase and creatine kinase to the OMM and for mitochondria-mediated apoptosis.     

Analysis of a secondary contact between divergent lineages of brown trout Salmo trutta L. from Duero basin using microsatellites and mtDNA RFLPs

The analysis of 12 microsatellite loci in 16 native populations of Salmo trutta from Duero basin evidenced a strong genetic differentiation in accordance with the existence of two divergent Atlantic mtDNA lineages, Atlantic (AT) and Duero (DU). These lineages were observed spatially segregated mainly in the Lower-course and in the inner part of the basin. Unlike previous isozyme information, microsatellite data suggested a more downstream location of the sharpest genetic divergence in Duero basin and a more complex structure in the inward area. Putative hybrid populations evidenced higher Hardy–Weinberg and gametic disequilibria than pure ones (Pisuerga, Lower-course), not explained by mixture due to differential immigration pattern across the basin. Hybridization indexes suggested a bimodal pattern of hybridization and a higher weight of Pisuerga region in the genetic composition of hybrid samples in accordance with mtDNA data. The results suggested a limited introgression between AT and DU lineages. Taking into account the time of divergence between both lineages, selection and/or genetic incompatibility appeared necessary to explain the genetic structure observed and the ancient location of DU lineage restricted to this area.