{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:41:04Z","timestamp":1760222464168,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T00:00:00Z","timestamp":1236729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Algorithms"],"abstract":"<jats:p>Many macromolecules, namely proteins, show functional substructures or epitopes defined by characteristic spatial arrangements of groups of specific atoms or residues. The identification of such substructures in a set of macromolecular 3D-structures solves an important problem in molecular biology as it allows the assignment of functions to molecular moieties and thus opens the possibility of a mechanistic understanding of molecular function. We have devised an algorithm that models a functional epitope formed by a group of atoms or residues as set of points in cartesian space with associated functional properties. The algorithm searches for similar epitopes in a database of structures by an efficient multistage comparison of distance sets in the epitope and in the structures from the database. The search results in a list of optimal matches and corresponding optimal superpositions of query epitope and matching epitopes from the database. The algorithm is discussed against the background of related approaches, and it is successfully tested in three application scenarios: global match of two homologous proteins, search for an epitope on a homologous protein, and finding matching epitopes in a protein database.<\/jats:p>","DOI":"10.3390\/a2010498","type":"journal-article","created":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T16:35:44Z","timestamp":1236789344000},"page":"498-517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Algorithm for Macromolecular Epitope Matching"],"prefix":"10.3390","volume":"2","author":[{"given":"Stanislav","family":"Jakuschev","sequence":"first","affiliation":[{"name":"Department of Bioinformatics, Centre for Medical Biotechnology, University of Duisburg-Essen, Universit\u00a8atsstrasse, 45117 Essen, Germany"}]},{"given":"Daniel","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Centre for Medical Biotechnology, University of Duisburg-Essen, Universit\u00a8atsstrasse, 45117 Essen, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2009,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"doi-asserted-by":"crossref","unstructured":"Gronwald, W., Hohm, T., and Hoffmann, D. (2008). Evolutionary Pareto-optimization of stably folding peptides. BMC Bioinformatics, 9.","key":"ref_2","DOI":"10.1186\/1471-2105-9-109"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1023\/A:1008194019144","article-title":"Computational Methods for the Structural Alignment of Molecules","volume":"14","author":"Lemmen","year":"2000","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/prot.10115","article-title":"Principles of Docking: An Overview of Search Algorithms and a Guide to Scoring Functions","volume":"47","author":"Halperin","year":"2002","journal-title":"Proteins"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/jmbi.1993.1489","article-title":"Protein Structure Comparison by Alignment of Distance Matrices","volume":"233","author":"Holm","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-2836(89)90084-3","article-title":"Protein Structure Alignment","volume":"208","author":"Taylor","year":"1989","journal-title":"J. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/protein\/7.1.39","article-title":"Molecular Surface Recognition by a Computer vision-based Technique","volume":"7","author":"Norel","year":"1994","journal-title":"Protein Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1023\/A:1021271615909","article-title":"Maximum Common Subgraph Isomorphism Algorithms for the Matching of Chemical Structures","volume":"16","author":"Raymond","year":"2002","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/jmbi.1994.1657","article-title":"A Graph-theoretic Approach to the Identification of Three-dimensional Patterns of Amino Acid Side-chains in Protein Structures","volume":"243","author":"Artymiuk","year":"1994","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1021\/ci60018a014","article-title":"Computer-Assisted Examination of Chemical Compounds for Structural Similarities","volume":"19","author":"Varkony","year":"1979","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1145\/362342.362367","article-title":"Algorithm 457: Finding All Cliques of an Undirected Graph","volume":"16","author":"Bron","year":"1973","journal-title":"Comm. of the ACM"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1107\/S0567739476001873","article-title":"A Solution for the Best Rotation to Relate Two Sets of Vectors","volume":"922","author":"Kabsch","year":"1976","journal-title":"Acta Cryst."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: Improving the Sensitivity of Progressive Multiple Sequence Alignment through Sequence Weighting, Positions-Specific Gap Penalties and Weight Matrix Choice","volume":"22","author":"Thompson","year":"1994","journal-title":"Nucl. Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.str.2003.09.016","article-title":"Structure of the Yeast Hst2 Protein Deacetylase in Ternary Complex with 2\u2019-O-Acetyl ADP Ribose and Histone Peptide","volume":"11","author":"Zhao","year":"2003","journal-title":"Structure"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1145\/321921.321925","article-title":"An Algorithm for Subgraph Isomorphism","volume":"16","author":"Ullmann","year":"1976","journal-title":"J. Assoc. Comput. Machinery"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jmb.2006.09.062","article-title":"How Different are Structurally Flexible and Rigid Binding Sites? Sequence and Structural Features Discriminating Proteins that Do and Do not Undergo Conformational Change upon Ligand Binding","volume":"365","author":"Gunasekaran","year":"2007","journal-title":"J. Mol. 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