Protein Geometry Database: a flexible engine to explore backbone conformations and their relationships to covalent geometry

The backbone bond lengths, bond angles, and planarity of a protein are influenced by the backbone conformation (φ,Ψ), but no tool exists to explore these relationships, leaving this area as a reservoir of untapped information about protein structure and function. The Protein Geometry Database (PGD) enables biologists to easily and flexibly query information about the conformation alone, the backbone geometry alone, and the relationships between them. The capabilities the PGD provides are valuable for assessing the uniqueness of observed conformational or geometric features in protein structure as well as discovering novel features and principles of protein structure. The PGD server is available at http://pgd.science.oregonstate.edu/ and the data and code underlying it are freely available to use and extend

Reduction Techniques for Graph Isomorphism in the Context of Width Parameters

We study the parameterized complexity of the graph isomorphism problem when parameterized by width parameters related to tree decompositions. We apply the following technique to obtain fixed-parameter tractability for such parameters. We first compute an isomorphism invariant set of potential bags for a decomposition and then apply a restricted version of the Weisfeiler-Lehman algorithm to solve isomorphism. With this we show fixed-parameter tractability for several parameters and provide a unified explanation for various isomorphism results concerned with parameters related to tree decompositions. As a possibly first step towards intractability results for parameterized graph isomorphism we develop an fpt Turing-reduction from strong tree width to the a priori unrelated parameter maximum degree.Comment: 23 pages, 4 figure

Peptide Bond Distortions from Planarity: New Insights from Quantum Mechanical Calculations and Peptide/Protein Crystal Structures

By combining quantum-mechanical analysis and statistical survey of peptide/protein structure databases we here report a thorough investigation of the conformational dependence of the geometry of peptide bond, the basic element of protein structures. Different peptide model systems have been studied by an integrated quantum mechanical approach, employing DFT, MP2 and CCSD(T) calculations, both in aqueous solution and in the gas phase. Also in absence of inter-residue interactions, small distortions from the planarity are more a rule than an exception, and they are mainly determined by the backbone ψ dihedral angle. These indications are fully corroborated by a statistical survey of accurate protein/peptide structures. Orbital analysis shows that orbital interactions between the σ system of Cα substituents and the π system of the amide bond are crucial for the modulation of peptide bond distortions. Our study thus indicates that, although long-range inter-molecular interactions can obviously affect the peptide planarity, their influence is statistically averaged. Therefore, the variability of peptide bond geometry in proteins is remarkably reproduced by extremely simplified systems since local factors are the main driving force of these observed trends. The implications of the present findings for protein structure determination, validation and prediction are also discussed

The nucleotide addition cycle of RNA polymerase is controlled by two molecular hinges in the Bridge Helix domain

Abstract Background Cellular RNA polymerases (RNAPs) are complex molecular machines that combine catalysis with concerted conformational changes in the active center. Previous work showed that kinking of a hinge region near the C-terminus of the Bridge Helix (BH-HC) plays a critical role in controlling the catalytic rate. Results Here, new evidence for the existence of an additional hinge region in the amino-terminal portion of the Bridge Helix domain (BH-HN) is presented. The nanomechanical properties of BH-HN emerge as a direct consequence of the highly conserved primary amino acid sequence. Mutations that are predicted to influence its flexibility cause corresponding changes in the rate of the nucleotide addition cycle (NAC). BH-HN displays functional properties that are distinct from BH-HC, suggesting that conformational changes in the Bridge Helix control the NAC via two independent mechanisms. Conclusions The properties of two distinct molecular hinges in the Bridge Helix of RNAP determine the functional contribution of this domain to key stages of the NAC by coordinating conformational changes in surrounding domains.</p

Scenario Analysis as a Tool for Informing the Design of Behaviour Change Interventions

This article presents the design process behind the specification of a behaviour change intervention method to promote energy saving. The amount of energy used for food preparation is highly influenced by people’s behaviours. A user-centred design approach based on scenario analysis was applied to provide understanding of context of use and specification of user requirements. This knowledge was applied to the design of behaviour change interventions to motivate sustainable behaviours

Using a conformation-dependent stereochemical library improves crystallographic refinement of proteins

A stereochemical library which defines the target values for main-chain bond lengths and angles as a function of the residue’s ϕ/ψ angles was tested in refinement. Use of this library allows the construction of models that conform to ideal geometry much better than previous libraries without degrading their fit to the diffraction data