Hierarchy of protein loop-lock structures: a new server for the decomposition of a protein structure into a set of closed loops

📝 Abstract

HoPLLS (Hierarchy of protein loop-lock structures) (http://leah.haifa.ac.il/~skogan/Apache/mydata1/main.html ) is a web server that identifies closed loops - a structural basis for protein domain hierarchy. The server is based on the loop-and-lock theory for structural organisation of natural proteins. We describe this web server, the algorithms for the decomposition of a 3D protein into loops and the results of scientific investigations into a structural “alphabet” of loops and locks.

💡 Analysis

HoPLLS (Hierarchy of protein loop-lock structures) (http://leah.haifa.ac.il/~skogan/Apache/mydata1/main.html ) is a web server that identifies closed loops - a structural basis for protein domain hierarchy. The server is based on the loop-and-lock theory for structural organisation of natural proteins. We describe this web server, the algorithms for the decomposition of a 3D protein into loops and the results of scientific investigations into a structural “alphabet” of loops and locks.

📄 Content

1 Hierarchy of protein loop-lock structures: a new server for the decomposition of a protein structure into a set of closed loops

Simon Kogan1*, Zakharia Frenkel1, 2, , Oleg Kupervasser1, 3* and Zeev Volkovich2**** 1Genome Diversity Center, Institute of Evolution, University of Haifa, Haifa 31905, Israel 2Department of Software Engineering, ORT Braude College, Karmiel, Israel
3Transist Video LLC, Skolkovo 119296, Russia

    *e-mail: simonkog@gmail.com 
  **e-mail: zakharf@research.haifa.ac.il 
***e-mail: olegkup@yahoo.com 

****e-mail: vlvolkov@braude.ac.il

Abstract HoPLLS (Hierarchy of protein loop-lock structures) (http://leah.haifa.ac.il/~skogan/Apache/mydata1/main.html ) is a web server that identifies closed loops - a structural basis for protein domain hierarchy. The server is based on the loop-and-lock theory for structural organisation of natural proteins. We describe this web server, the algorithms for the decomposition of a 3D protein into loops and the results of scientific investigations into a structural “alphabet” of loops and locks.

Keywords: structural alphabet, loop-lock structure, web server, protein, amino acids

Introduction
Several years ago, it was revealed that the majority of known natural globular proteins can be considered to be combinations of closed loops of an approximately standard size (25-35 amino acids (aa)). This discovery was based on polypeptide chain statistics [1]. The discovery was applied toward the understanding of the protein folding mechanism [2, 3], protein structural organisation [2, 4] and protein evolution [5, 6]. It was proposed that closed loops of an optimal size were an important stage in protein evolution. At that particular stage, the natural proteins were small molecules (25-35 amino acids in size) in which the turning of the backbone back onto itself (i.e., the formation of closed loops) could be an important selective advantage that provided stability to the molecule. In the next stage, these small proteins made of one closed loop united to form modern-sized domains (50-300 aa). The main hypothesis is that the closed loops, being elementary protein modules, at least partially conserved their ancestral structural and functional properties in modern proteins. Presumably, such modules can be classified into a limited number of families, which each originate from a corresponding, early ancestor protein formed from a single closed-loop protein. Such types of primary conserved families have already been described [7, 8]. Thus, the presentation of proteins as a set of closed-loop, conserved, standard- sized modules would be very useful for protein characterisation and classification and for understanding protein evolution.
The first, pared-down version of the site was created in 2005. Recently, the site was considerably improved and a new, important, theoretical investigation related to the topic of the site was performed. The improvement and investigation were the reasons to write this paper. The first paper about the web server (DHcL), which implements the decomposition of a protein into a set of closed loops, was published in 2008 [9]. This server demonstrates a set of the best loops (with the smallest distances between ends and allowing a small overlap of 5 aa)

2 rather than the optimal decomposition of non-overlapping loops (as our web server does). We will discuss the differences in detail in the Results section. In this paper, the manual for HoPLLS (Hierarchy of protein loop-lock structures) is given, and the applied algorithms are described.
We also present the results of the application of HoPLLS to the creation of a full library of protein-building, closed-loop elements. This data can be used to find a new structural alphabet [7, 8] based on the conserved modules and can be used for protein annotation and comparison.

Methods

1. Algorithms for decomposing the protein structure into loop-like elements

In the loop-lock representation, we consider a protein to be a set of closed loops [5-7]. We name the place where the ends of a loop meet each other a van der Waals lock [10, 11]. The lock area is +/-Lr (“the lock radius” [10]) relative to the position of each end of the loop. Lr is equal to 1 amino acid, 2 amino acids or 3 amino acids. In this paper, we present algorithms to decompose a protein into a set of non-overlapping loops. We implemented two loop decomposition approaches.
The first approach (the geometrical algorithm) is based on minimising lock distances (distance between two ends of the loop) and maximising coverage of the protein with loops. We give priority to loops with smaller distances between the Cα atoms at the ends of the loops and with longer lengths.
The second approach (the physical algorithm) is based on the loop density criteria, i.e., finding a set of loops with the maximum number of internal links (not only links at the ends).

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