Evidence for Non-Random Hydrophobicity Structures in Protein Chains

The question of whether proteins originate from random sequences of amino acids is addressed. A statistical analysis is performed in terms of blocked and random walk values formed by binary hydrophobic assignments of the amino acids along the protein chains. Theoretical expectations of these variables from random distributions of hydrophobicities are compared with those obtained from functional proteins. The results, which are based upon proteins in the SWISS-PROT data base, convincingly show that the amino acid sequences in proteins differ from what is expected from random sequences in a statistical significant way. By performing Fourier transforms on the random walks one obtains additional evidence for non-randomness of the distributions. We have also analyzed results from a synthetic model containing only two amino-acid types, hydrophobic and hydrophilic. With reasonable criteria on good folding properties in terms of thermodynamical and kinetic behavior, sequences that fold well are isolated. Performing the same statistical analysis on the sequences that fold well indicates similar deviations from randomness as for the functional proteins. The deviations from randomness can be interpreted as originating from anticorrelations in terms of an Ising spin model for the hydrophobicities. Our results, which differ from previous investigations using other methods, might have impact on how permissive with respect to sequence specificity the protein folding process is -- only sequences with non-random hydrophobicity distributions fold well. Other distributions give rise to energy landscapes with poor folding properties and hence did not survive the evolution.Comment: 16 pages, 8 Postscript figures. Minor changes, references adde

Design of Sequences with Good Folding Properties in Coarse-Grained Protein Models

Background: Designing amino acid sequences that are stable in a given target structure amounts to maximizing a conditional probability. A straightforward approach to accomplish this is a nested Monte Carlo where the conformation space is explored over and over again for different fixed sequences, which requires excessive computational demand. Several approximate attempts to remedy this situation, based on energy minimization for fixed structure or high-$T$ expansions, have been proposed. These methods are fast but often not accurate since folding occurs at low $T$. Results: We develop a multisequence Monte Carlo procedure, where both sequence and conformation space are simultaneously probed with efficient prescriptions for pruning sequence space. The method is explored on hydrophobic/polar models. We first discuss short lattice chains, in order to compare with exact data and with other methods. The method is then successfully applied to lattice chains with up to 50 monomers, and to off-lattice 20-mers. Conclusions: The multisequence Monte Carlo method offers a new approach to sequence design in coarse-grained models. It is much more efficient than previous Monte Carlo methods, and is, as it stands, applicable to a fairly wide range of two-letter models.Comment: 23 pages, 7 figure

77 Million Reasons to Give Millennials a Chance

In this short and delightful response, Anders Peterson adds his own reflections on being a Millennial

Local Interactions and Protein Folding: A 3D Off-Lattice Approach

The thermodynamic behavior of a three-dimensional off-lattice model for protein folding is probed. The model has only two types of residues, hydrophobic and hydrophilic. In absence of local interactions, native structure formation does not occur for the temperatures considered. By including sequence independent local interactions, which qualitatively reproduce local properties of functional proteins, the dominance of a native state for many sequences is observed. As in lattice model approaches, folding takes place by gradual compactification, followed by a sequence dependent folding transition. Our results differ from lattice approaches in that bimodal energy distributions are not observed and that high folding temperatures are accompanied by relatively low temperatures for the peak of the specific heat. Also, in contrast to earlier studies using lattice models, our results convincingly demonstrate that one does not need more than two types of residues to generate sequences with good thermodynamic folding properties in three dimensions.Comment: 18 pages, 11 Postscript figure

Recreation in Swedish agricultural areas – public attitudes to multifunctional greenway designs

Recreation in the agricultural landscape of SW Sweden is limited in several ways. There is little else than agricultural fields and urbanised areas, and outdoor recreation is limited to a few, small areas. Although the Swedish Right of Public Access allows for accessing the agricultural fields by foot, this is not allowed during periods when there is standing crop. Apart from this, the fields are not particularly inviting, since the winds are continuous and often harsh, and walking on the muddy fields is not comfortable. It should be stressed that this is the everyday landscape for a growing peri-urban population. Furthermore, the homogenisation process that this landscape has undergone for the last five or six decades has also resulted in reduced biodiversity, which further reduces the attraction of the landscape. To make the agricultural landscape more accessible for recreation, some landowners and municipalities have established narrow (3–6 meters wide) greenways along field margins. Since these greenways are primarily aimed at recreation, they are not particularly well suited for plant and animal wildlife, and they are generally too narrow to allow for different types of recreation, such as riding at the same time as walking with dogs or prams. A further drawback with the existing greenways is their lack of protection against the continuous winds in the open landscape. Since these aspects were not considered when the greenways were established, it is probable that simple modifications of the design could satisfy more needs. It is, however, unclear whether such a development would be acceptable and desirable to the involved users and landowners, and whether it could gain support from the authorities

A direct limit on the turbulent velocity of the intracluster medium in the core of Abell 1835 from XMM-Newton

We examine deep XMM-Newton Reflection Grating Spectrometer (RGS) observations of the X-ray luminous galaxy cluster A1835. For the first time in a galaxy cluster we place direct limits on turbulent broadening of the emission lines. This is possible because the coolest X-ray emitting gas in the cluster, which is responsible for the lines, occupies a small region within the core. The most conservative determination of the 90 per cent upper limit on line-of-sight, non-thermal, velocity broadening is 274 km/s, measured from the emission lines originating within 30 kpc radius. The ratio of turbulent to thermal energy density in the core is therefore less than 13 per cent. There are no emission lines in the spectrum showing evidence for gas below ~3.5 keV. We examine the quantity of gas as a function of temperature and place a limit of 140 Msun/yr (90 per cent) for gas cooling radiatively below 3.85 keV.Comment: 5 pages, accepted by MNRAS, includes minor change suggested by refere