eProS—a database and toolbox for investigating protein sequence–structure–function relationships through energy profiles

Abstract

Gaining information about structural and functional features of newly identified proteins is often a difficult task. This information is crucial for understanding sequence–structure–function relationships of target proteins and, thus, essential in comprehending the mechanisms and dynamics of the molecular systems of interest. Using protein energy profiles is a novel approach that can contribute in addressing such problems. An energy profile corresponds to the sequence of energy values that are derived from a coarse-grained energy model. Energy profiles can be computed from protein structures or predicted from sequences. As shown, correspondences and dissimilarities in energy profiles can be applied for investigations of protein mechanics and dynamics. We developed eProS (energy profile suite, freely available at http://bioservices.hs-mittweida.de/Epros/), a database that provides ∼76 000 pre-calculated energy profiles as well as a toolbox for addressing numerous problems of structure biology. Energy profiles can be browsed, visualized, calculated from an uploaded structure or predicted from sequence. Furthermore, it is possible to align energy profiles of interest or compare them with all entries in the eProS database to identify significantly similar energy profiles and, thus, possibly relevant structural and functional relationships. Additionally, annotations and cross-links from numerous sources provide a broad view of potential biological correspondences.

eProS – A Bioinformatics Knowledgebase, Toolbox and Database for Characterizing Protein Function

“…Hence, implemented alignment algorithms supply an automated methodology for deducing overlapping and mismatching regions. Such information can be valuable in understanding functional similarities and dissimilarities [9]. Energy profile and alignment visualizations provide an intuitive presentation for working with the protein data of interest, which can be uploaded as PDB (Protein Data Bank [13]) files or as energy profile files (downloaded from eProS after previous calculations), specified by PDB IDs, or as protein sequences.…”

“…The first conducts alignment computations and alignment significance testing to each entry in the database. This exhaustive strategy is guaranteed to find the best global or local overlap and thus performs best with respect to sensitivity [9]. However, required search times are generally long, due to the time complexity of O(pnD), where n is the length of the query energy profile (equals the size of the corresponding protein chain), D is the total number of energy profiles in the database, and p is a query-dependent variable used for testing alignment significance.…”

“…Recent studies have demonstrated that sequences of energy values, referred to as energy profiles, obtained from protein structures using fine and coarse-grained energy models can be used to characterize protein functionality and structural features [10,11,7,9]. Mrozek et al had introduced a dynamic programming approach for generating energy profile alignments [10,11].…”

“…To implement an automated energy profile generation pipeline for large-scale analyses thus becomes challenging. However, such analyses can be of interest in structural biology, as entire protein folds and families can be investigated in the focus of characterizing and understanding the energetic features that determine protein structure, stability and function [10,11,7,9].…”

“…As shown by Heinke et al [9,7,8] this model is capable to cope with the task of characterizing protein structure changes caused by protein-environment interactions. In these studies energy profiling was employed to investigate energetic changes in models of mutant aquaporin 2 structures -a key membrane protein in maintaining the body's water balance.…”