A New Simulated Annealing Algorithm for the Multiple Sequence Alignment Problem: The approach of Polymers in a Random Media

We proposed a probabilistic algorithm to solve the Multiple Sequence Alignment problem. The algorithm is a Simulated Annealing (SA) that exploits the representation of the Multiple Alignment between $D$ sequences as a directed polymer in $D$ dimensions. Within this representation we can easily track the evolution in the configuration space of the alignment through local moves of low computational cost. At variance with other probabilistic algorithms proposed to solve this problem, our approach allows for the creation and deletion of gaps without extra computational cost. The algorithm was tested aligning proteins from the kinases family. When D=3 the results are consistent with those obtained using a complete algorithm. For $D>3$ where the complete algorithm fails, we show that our algorithm still converges to reasonable alignments. Moreover, we study the space of solutions obtained and show that depending on the number of sequences aligned the solutions are organized in different ways, suggesting a possible source of errors for progressive algorithms.Comment: 7 pages and 11 figure

TOPSAN: a collaborative annotation environment for structural genomics

<p>Abstract</p> <p>Background</p> <p>Many protein structures determined in high-throughput structural genomics centers, despite their significant novelty and importance, are available only as PDB depositions and are not accompanied by a peer-reviewed manuscript. Because of this they are not accessible by the standard tools of literature searches, remaining underutilized by the broad biological community.</p> <p>Results</p> <p>To address this issue we have developed TOPSAN, The Open Protein Structure Annotation Network, a web-based platform that combines the openness of the wiki model with the quality control of scientific communication. TOPSAN enables research collaborations and scientific dialogue among globally distributed participants, the results of which are reviewed by experts and eventually validated by peer review. The immediate goal of TOPSAN is to harness the combined experience, knowledge, and data from such collaborations in order to enhance the impact of the astonishing number and diversity of structures being determined by structural genomics centers and high-throughput structural biology.</p> <p>Conclusions</p> <p>TOPSAN combines features of automated annotation databases and formal, peer-reviewed scientific research literature, providing an ideal vehicle to bridge a gap between rapidly accumulating data from high-throughput technologies and a much slower pace for its analysis and integration with other, relevant research.</p

Simplified amino acid alphabets based on deviation of conditional probability from random background

The primitive data for deducing the Miyazawa-Jernigan contact energy or BLOSUM score matrix consists of pair frequency counts. Each amino acid corresponds to a conditional probability distribution. Based on the deviation of such conditional probability from random background, a scheme for reduction of amino acid alphabet is proposed. It is observed that evident discrepancy exists between reduced alphabets obtained from raw data of the Miyazawa-Jernigan's and BLOSUM's residue pair counts. Taking homologous sequence database SCOP40 as a test set, we detect homology with the obtained coarse-grained substitution matrices. It is verified that the reduced alphabets obtained well preserve information contained in the original 20-letter alphabet.Comment: 9 pages,3figure

TOPSAN: use of a collaborative environment for annotating, analyzing and disseminating data on JCSG and PSI structures

Specific use cases of TOPSAN, an innovative collaborative platform for creating, sharing and distributing annotations and insights about protein structures, such as those determined by high-throughput structural genomics in the Protein Structure Initiative (PSI), are described. TOPSAN is the main annotation platform for JCSG structures and serves as a conduit for initiating collaborations with the biological community, as illustrated in this special issue of Acta Crystallographica Section F. Developed at the JCSG with the goal of opening a dialogue on the novel protein structures with the broader biological community, TOPSAN is a unique tool for fostering distributed collaborations and provides an efficient pathway to peer-reviewed publications

Early surgical intervention among patients with acute central cord syndrome is not associated with higher mortality and morbidity

Background: Conflicting reports exist regarding mortality and morbidity of early surgical decompression in the setting of acute central cord syndrome (ACS) in multisystem trauma despite evidence of improved neurological outcomes. Consequently, optimal decompression timing in ACS in multisystem trauma patients remains controversial. This study aims to determine the association between early surgery for acute traumatic central cord and all-cause mortality among multisystem trauma patients in the National Trauma Data Bank (NTDB) using propensity score matching. Methods: We used the NTDB (years 2011-2014) to perform a retrospective cohort study, which included patients \u3e18 years, with ACS (identified using ICD-9 coding). Collected patient data included demographics, surgery timing (≤24 hours, \u3e24 hours), injury mechanism, Charlson comorbidity index (CCI), injury severity score (ISS), serious adverse events (SAE). Logistic regression and propensity matching were used to investigate the relationship between surgery timing and subsequent inpatient mortality. Results: We identified 2,379 traumatic ACS patients. This group was 79.3% male with an average age of 56.3±15.2. They had an average ISS of 19.5±9.0 and mortality rate of 3.0% (n=72). A total of 731 (30.7%) patients underwent surgery for ACS within 24 hours. Univariate analysis did not show a significantly higher mortality rate in the early versus late surgery groups (3.8% Conclusions: Early surgical intervention does not appear to be associated with increased mortality among ACS patients unlike previously suggested. We theorize that survival noted within the NTDB is confounded by factors including existing comorbidities and multisystem trauma, rather than surgical timing. Delaying definitive surgical care may predispose patients to worsened greater neurological morbidity

TOPSAN: a dynamic web database for structural genomics

The Open Protein Structure Annotation Network (TOPSAN) is a web-based collaboration platform for exploring and annotating structures determined by structural genomics efforts. Characterization of those structures presents a challenge since the majority of the proteins themselves have not yet been characterized. Responding to this challenge, the TOPSAN platform facilitates collaborative annotation and investigation via a user-friendly web-based interface pre-populated with automatically generated information. Semantic web technologies expand and enrich TOPSAN’s content through links to larger sets of related databases, and thus, enable data integration from disparate sources and data mining via conventional query languages. TOPSAN can be found at http://www.topsan.org

Deriving amino acid contact potentials from their frequencies of occurence in proteins: a lattice model study

The possibility of deriving the contact potentials between amino acids from their frequencies of occurence in proteins is discussed in evolutionary terms. This approach allows the use of traditional thermodynamics to describe such frequencies and, consequently, to develop a strategy to include in the calculations correlations due to the spatial proximity of the amino acids and to their overall tendency of being conserved in proteins. Making use of a lattice model to describe protein chains and defining a "true" potential, we test these strategies by selecting a database of folding model sequences, deriving the contact potentials from such sequences and comparing them with the "true" potential. Taking into account correlations allows for a markedly better prediction of the interaction potentials

Discrete kink dynamics in hydrogen-bonded chains I: The one-component model

We study topological solitary waves (kinks and antikinks) in a nonlinear one-dimensional Klein-Gordon chain with the on-site potential of a double-Morse type. This chain is used to describe the collective proton dynamics in quasi-one-dimensional networks of hydrogen bonds, where the on-site potential plays role of the proton potential in the hydrogen bond. The system supports a rich variety of stationary kink solutions with different symmetry properties. We study the stability and bifurcation structure of all these stationary kink states. An exactly solvable model with a piecewise ``parabola-constant'' approximation of the double-Morse potential is suggested and studied analytically. The dependence of the Peierls-Nabarro potential on the system parameters is studied. Discrete travelling-wave solutions of a narrow permanent profile are shown to exist, depending on the anharmonicity of the Morse potential and the cooperativity of the hydrogen bond (the coupling constant of the interaction between nearest-neighbor protons).Comment: 12 pages, 20 figure

Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination

The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination-dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation. For randomly sampled representative substrates, we confirmed that their cellular stability is in agreement with our screening prediction. Importantly, the two groups display unique features: monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways, and, in humans, are structurally less disordered. We suggest that monoubiquitination-dependent degradation is more widespread than assumed previously, and plays key roles in various cellular processes

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe