title: γ-TEMPy: Simultaneous Fitting of Components in 3D-EM Maps of Their Assembly Using a Genetic Algorithm.
abstract: We have developed a genetic algorithm for building macromolecular complexes using only a 3D-electron microscopy density map and the atomic structures of the relevant components. For efficient sampling the method uses map feature points calculated by vector quantization. The fitness function combines a mutual information score that quantifies the goodness of fit with a penalty score that helps to avoid clashes between components. Testing the method on ten assemblies (containing 3-8 protein components) and simulated density maps at 10, 15, and 20 Å resolution resulted in identification of the correct topology in 90%, 70%, and 60% of the cases, respectively. We further tested it on four assemblies with experimental maps at 7.2-23.5 Å resolution, showing the ability of the method to identify the correct topology in all cases. We have also demonstrated the importance of the map feature-point quality on assembly fitting in the lack of additional experimental information.
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK.
authors.forename: Arun Prasad
authors.initials: AP
authors.lastname: Pandurangan
authors.affiliation: Division of Structural Biology, Oxford Particle Imaging Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Daven
authors.initials: D
authors.lastname: Vasishtan
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, 1050 Childs Way, RRI413E, Los Angeles, CA 90089, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Alber
authors.affiliation: Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK. Electronic address: m.topf@cryst.bbk.ac.uk.
authors.forename: Maya
authors.initials: M
authors.lastname: Topf
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D005838:Genotype; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D012984:Software