TMBETA-GENOME: database for annotated β-barrel membrane proteins in genomic sequences

We have developed the database, TMBETA-GENOME, for annotated β-barrel membrane proteins in genomic sequences using statistical methods and machine learning algorithms. The statistical methods are based on amino acid composition, reside pair preference and motifs. In machine learning techniques, the combination of amino acid and dipeptide compositions has been used as main attributes. In addition, annotations have been made using the criterion based on the identification of β-barrel membrane proteins and exclusion of globular and transmembrane helical proteins. A web interface has been developed for identifying the annotated β-barrel membrane proteins in all known genomes. The users have the feasibility of selecting the genome from the three kingdoms of life, archaea, bacteria and eukaryote, and five different methods. Further, the statistics for all genomes have been provided along with the links to different algorithms and related databases. It is freely available at

Outer membrane proteins can be simply identified using secondary structure element alignment

<p>Abstract</p> <p>Background</p> <p>Outer membrane proteins (OMPs) are frequently found in the outer membranes of gram-negative bacteria, mitochondria and chloroplasts and have been found to play diverse functional roles. Computational discrimination of OMPs from globular proteins and other types of membrane proteins is helpful to accelerate new genome annotation and drug discovery.</p> <p>Results</p> <p>Based on the observation that almost all OMPs consist of antiparallel β-strands in a barrel shape and that their secondary structure arrangements differ from those of other types of proteins, we propose a simple method called SSEA-OMP to identify OMPs using secondary structure element alignment. Through intensive benchmark experiments, the proposed SSEA-OMP method is better than some well-established OMP detection methods.</p> <p>Conclusions</p> <p>The major advantage of SSEA-OMP is its good prediction performance considering its simplicity. The web server implements the method is freely accessible at <url>http://protein.cau.edu.cn/SSEA-OMP/index.html</url>.</p

MEDELLER: homology-based coordinate generation for membrane proteins

Motivation: Membrane proteins (MPs) are important drug targets but knowledge of their exact structure is limited to relatively few examples. Existing homology-based structure prediction methods are designed for globular, water-soluble proteins. However, we are now beginning to have enough MP structures to justify the development of a homology-based approach specifically for them

In silico local structure approach: A case study on Outer Membrane Proteins.

International audienceThe detection of Outer Membrane Proteins (OMP) in whole genomes is an actual question, their sequence characteristics have thus been intensively studied. This class of protein displays a common beta-barrel architecture, formed by adjacent antiparallel strands. However, due to the lack of available structures, few structural studies have been made on this class of proteins. Here we propose a novel OMP local structure investigation, based on a structural alphabet approach, i.e., the decomposition of 3D structures using a library of four-residue protein fragments. The optimal decomposition of structures using hidden Markov model results in a specific structural alphabet of 20 fragments, six of them dedicated to the decomposition of beta-strands. This optimal alphabet, called SA20-OMP, is analyzed in details, in terms of local structures and transitions between fragments. It highlights a particular and strong organization of beta-strands as series of regular canonical structural fragments. The comparison with alphabets learned on globular structures indicates that the internal organization of OMP structures is more constrained than in globular structures. The analysis of OMP structures using SA20-OMP reveals some recurrent structural patterns. The preferred location of fragments in the distinct regions of the membrane is investigated. The study of pairwise specificity of fragments reveals that some contacts between structural fragments in beta-sheets are clearly favored whereas others are avoided. This contact specificity is stronger in OMP than in globular structures. Moreover, SA20-OMP also captured sequential information. This can be integrated in a scoring function for structural model ranking with very promising results. Proteins 2007. (c) 2007 Wiley-Liss, Inc

DEVELOPMENT, VALIDATION, AND APPLICATION OF ANALYTICAL METHODS FOR CHARACTERIZING ADSORBED PROTEIN ORIENTATION, CONFORMATION, AND BIOACTIVITY

The structure and bioactivity of adsorbed proteins are tightly interrelated and play a key role in their interaction with the surrounding environment. These factors are of critical importance in many biotechnological applications. However, because the bioactive state of an adsorbed protein is a function of the orientation, conformation, and accessibility of its bioactive site(s), the isolated determination of just one or two of these factors will typically not be sufficient to understand the structure-function relationships of the adsorbed layer. Rather a combination of methods is needed to address each of these factors in a synergistic manner to provide a complementary dataset to characterize and understand the bioactive state of adsorbed protein. In this research, I describe and demonstrate the potential of a set of complementary methods: (a) circular dichroism spectropolarimetry to determine adsorption-induced changes in protein secondary structure, (b) amino-acid labeling/mass spectrometry to assess adsorbed protein orientation and tertiary structure by monitoring adsorption-induced changes in a residue\u27s solvent accessibility, and (c) bioactivity assays to assess adsorption-induced changes in a protein\u27s bioactivity. Subsequently, the developed techniques were applied to characterize: (a) the role of protein-protein interactions (PPI) in influencing the structure and activity of a protein during its layer formation, and (b) the influence of chemical excipients on the stability and potency of an adsorbed layer of protein. While the effect of PPI on the initial adsorbed configuration and bioactivity of a protein layer varied with the type of adsorbent surface and protein composition, the effects of chemical excipients on the stability and potency of an adsorbed protein layer primarily depended on its initial adsorbed configuration. From an evaluation of the structure-function relationship within these adsorbed layers, their bioactivity was found to reduce in direct proportion to the disruption in protein structure in majority of the systems studied. Although, the presented techniques do have the limitation of being low in resolution, the techniques developed in this study do provide insights into the molecular processes influencing the structure-function relationships of adsorbed protein that were previously unknown