Identification of hot regions in protein-protein interactions by sequential pattern mining

<p>Abstract</p> <p>Background</p> <p>Identification of protein interacting sites is an important task in computational molecular biology. As more and more protein sequences are deposited without available structural information, it is strongly desirable to predict protein binding regions by their sequences alone. This paper presents a pattern mining approach to tackle this problem. It is observed that a functional region of protein structures usually consists of several peptide segments linked with large wildcard regions. Thus, the proposed mining technology considers large irregular gaps when growing patterns, in order to find the residues that are simultaneously conserved but largely separated on the sequences. A derived pattern is called a cluster-like pattern since the discovered conserved residues are always grouped into several blocks, which each corresponds to a local conserved region on the protein sequence.</p> <p>Results</p> <p>The experiments conducted in this work demonstrate that the derived long patterns automatically discover the important residues that form one or several hot regions of protein-protein interactions. The methodology is evaluated by conducting experiments on the web server MAGIIC-PRO based on a well known benchmark containing 220 protein chains from 72 distinct complexes. Among the tested 218 proteins, there are 900 sequential blocks discovered, 4.25 blocks per protein chain on average. About 92% of the derived blocks are observed to be clustered in space with at least one of the other blocks, and about 66% of the blocks are found to be near the interface of protein-protein interactions. It is summarized that for about 83% of the tested proteins, at least two interacting blocks can be discovered by this approach.</p> <p>Conclusion</p> <p>This work aims to demonstrate that the important residues associated with the interface of protein-protein interactions may be automatically discovered by sequential pattern mining. The detected regions possess high conservation and thus are considered as the computational hot regions. This information would be useful to characterizing protein sequences, predicting protein function, finding potential partners, and facilitating protein docking for drug discovery.</p

[[alternative]]Integral Points on Elliptic Curves

[[abstract]]Let E be an elliptic curve over Q. A well-known theorem of Siegel asserts that the number of integral points on E is finite. So, for a given elliptic curve E over Q, it would be interesting to find all the integral points. In [Za], Zagier describes several methods for explicitly computing large integral points on elliptic curves defined over Q. In this thesis, follow the line of [ST1], we shall discuss a method of computing all the integral points on an elliptic curve over Q under the hypothesis that a basis for the free part of the Mordell-Weil group is given. In [ST1], R. J. Stroeker and N. Tzanakis adopt a natural approach, in which the linear relation between an integral point and the generators of the free part of the Mordell-Weil group is directly transformed into a linear form in elliptic logarithms. In order to produce upper bounds for the coefficients in the original linear relation, we need an effective lower bound for the linear form in elliptic logarithms. Thanks to S. David [D, Th&acute;eor`eme 2.1], such an explicit lower bound was established. The upper bound for the linear form in elliptic logarithms was established in [ST1], where one needs to deduce an upper bound for the function (see section 2.2) described in [Za]. In section 2, we discuss three main inequalities which are given in [ST1], as well as a special case of David’s lower bound which is described in the appendix of [ST1]. In section 3, by combining the main inequalities and David’s lower bound, we obtain an upper bound for the coefficients in the original linear relation. However, the upper bound obtained in section 3 is too large to search all the integral points. So, we need to apply the LLL-reduction procedure to reduce the upper bound of the coefficients. This will constitute section 4. In the final section, some examples are given.

The Role of Dehydroepiandrosterone Levels on Physiologic Acclimatization to Chronic Mountaineering Activity

[[abstract]]Lee, Wen-Chih, Shu-Man Chen, Min-Chieh Wu, Chien-Wen Hou, Yu-Chiang Lai, Yi-Hung Laio, Chin-Hung Lin, and Chia-Hua Kuo. The role of dehydroepiandrosterone levels on physiologic acclimatization to chronic mountaineering activity. High Alt. Med. Biol. 7:228–236, 2006.—Previous studies have reported that glucose tolerance can be improved by short-term altitude living and activity. However, not all literature agrees that insulin sensitivity is increased at altitude. The present study investigated the effect of a 25-day mountaineering activity on glucose tolerance and its relation to serum levels of dehydroepiandrosterone-sulfate (DHEA-S) and tumor necrosis factor-α (TNF-α) in 12 male subjects. On day 3 at altitude, we found that serum DHEAS was reduced in the subjects with initially greater DHEA-S value, whereas the subjects with initially lower DHEA-S remained unchanged. To further elucidate the role of DHEA-S in acclimatization to mountaineering activity, all subjects were then divided into lower and upper halves according to their sea-level DHEA-S concentrations: low DHEA-S (n = 6) and high DHEA-S groups (n = 6). Glucose tolerance, insulin level, and the normal physiologic responses to altitude exposure, including hematocrit, hemoglobin, erythropoietin (EPO), and cortisol were measured. We found that glucose and insulin concentrations on an oral glucose tolerance test were significantly lowered by the mountaineering activity only in the high DHEA-S group. Similarly, hematocrit and hemoglobin concentration in altitude were increased only in the high DHEA-S group. In contrast, the low DHEA-S subjects exhibited an EPO value at sea level and altitude greater than the high DHEA-S group, suggesting an EPO resistance. The findings of the study imply that DHEA-S is essential for physiologic acclimatization to mountaineering challenge

The pattern discovered for the PDB chain PDB:, chain A, where the pattern blocks are shown in with different blocks plotted in distinct colors, protein LCI in , and zinc ions in crimson spheres

<p><b>Copyright information:</b></p><p>Taken from "Identification of hot regions in protein-protein interactions by sequential pattern mining"</p><p>http://www.biomedcentral.com/1471-2105/8/S5/S8</p><p>BMC Bioinformatics 2007;8(Suppl 5):S8-S8.</p><p>Published online 24 May 2007</p><p>PMCID:PMC1892096.</p><p></p> This maximum-size pattern hits the contact regions when interacting with the protein LCI, where the ligand GLU is plotted in representation and colored in CPK mode

Example used to illustrate how the patterns generated by MAGIIC-PRO facilitate the study of identifying hot regions

<p><b>Copyright information:</b></p><p>Taken from "Identification of hot regions in protein-protein interactions by sequential pattern mining"</p><p>http://www.biomedcentral.com/1471-2105/8/S5/S8</p><p>BMC Bioinformatics 2007;8(Suppl 5):S8-S8.</p><p>Published online 24 May 2007</p><p>PMCID:PMC1892096.</p><p></p> The protruding residue Arg15 of 5L15 (chain I) falls in the first block of the derived pattern and the structurally conserved residues in the complemented pocket of VIIa (chain H) can be found in the three blocks of the derived pattern. The patterns are plotted as representation on the structure and colored in the same way as in their regular expression form

Representation of the GrpE-DnaKATPase complex PDB: with the pattern found by MAGIIC-PRO for GrpE protein

<p><b>Copyright information:</b></p><p>Taken from "Identification of hot regions in protein-protein interactions by sequential pattern mining"</p><p>http://www.biomedcentral.com/1471-2105/8/S5/S8</p><p>BMC Bioinformatics 2007;8(Suppl 5):S8-S8.</p><p>Published online 24 May 2007</p><p>PMCID:PMC1892096.</p><p></p> The pattern is plotted as , GrpE as , and DnaKATPase as display