Blind testing of cross‐linking/mass spectrometry hybrid methods in CASP11

• DOI: 10.1002/prot.25028
• Publication Date: 2016-03-06T08:45:54Z
• Authors: Michael Schneider; Adam Belsom; Juri Rappsilber; Oliver Brock
• Keywords: Models, Molecular; 0301 basic medicine; Protein Folding; Ultraviolet Rays; International Cooperation; Succinimides; Mass Spectrometry; Protein Structure, Secondary; 03 medical and health sciences; ddc:570; blind test; Computer Simulation; Protein Interaction Domains and Motifs; Amino Acid Sequence; Databases, Protein; mass spectrometry; Internet; Models, Statistical; Computational Biology; Proteins; Articles; hybrid methods; protein structure prediction; Cross-Linking Reagents; CASP; Sequence Alignment; Algorithms; Software; 570 Biowissenschaften; Biologie; cross-linking

ABSTRACT Hybrid approaches combine computational methods with experimental data. The information contained in the data can be leveraged to probe structure of proteins otherwise elusive methods. Compared methods, structures produced by hybrid exhibit some degree validation. In spite these advantages, most have not yet been validated blind tests, hampering their development. Here, we describe first test a specific cross‐link based method CASP. This was coordinated CASP organizers and utilized novel, high‐density cross‐linking/mass‐spectrometry (CLMS) approach that is able collect CLMS matter days. protocol developed Rappsilber laboratory. exploits chemistry highly reactive, photoactivatable cross‐linker produce an order magnitude more cross‐links than homobifunctional cross‐linkers. laboratory generated on this protocol, submitted which then released CASP11 prediction groups separate, assisted modeling experiment. We did observe clear improvement models, presumably because properties data—uncertainty identification residue‐residue assignment, uneven distribution over protein—were largely unknown were tailored kind also suggest modifications CLMS‐CASP experiment discuss importance rigorous testing development Proteins 2016; 84(Suppl 1):152–163. © 2016 Authors Proteins: Structure, Function, Bioinformatics Published Wiley Periodicals, Inc.