caa a22 4500 445821086 CHVBK 20180317145244.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00239-011-9454-3 doi (NATIONALLICENCE)springer-10.1007/s00239-011-9454-3 Fast Side Chain Replacement in Proteins Using a Coarse-Grained Approach for Evaluating the Effects of Mutation During Evolution [Elektronische Daten] [Johan Grahnen, Jan Kubelka, David Liberles] For high-throughput structural genomic and evolutionary bioinformatics approaches, there is a clear need for fast methods to evaluate substitutions structurally. Coarse-grained methods are both powerful and fast, and a coarse-grained approach to position the substituted side chains is presented. Through the application of a coarse-grained method, a speed-up on the single- residue replacement, of at least sevenfold is achieved compared with modern all-atom approaches. At the same time, this approach maintains a small median RMSD from the leading all-atom approach (as measured in coarse-grained space), and predicts the conformation of point mutants with similar accuracy and generates biologically realistic side chain angles. This method is also substantially more predictable in its run time, making it useful for high-throughput studies of protein structural evolution. To demonstrate the utility of this method, it has been implemented in a forward simulation of sequences threaded through the SH2 domains, with selective pressures to fold and bind specifically. The relative substitution rates across the protein structure and at the binding interface are reflective of those observed in SH2 domain evolution. The algorithm has been implemented in C++, with the source code and binaries (currently supported for Linux systems) freely available as SARA at http://www.wyomingbioinformatics.org/LiberlesGroup/SARA . Springer Science+Business Media, LLC, 2011 Molecular evolution nationallicence Sequence simulation nationallicence Homology modeling nationallicence Sequence-structure-function relationships nationallicence Amino acid substitution nationallicence Grahnen Johan Department of Molecular Biology, University of Wyoming, 82071, Laramie, WY, USA aut Kubelka Jan Department of Chemistry, University of Wyoming, 82071, Laramie, WY, USA aut Liberles David Department of Molecular Biology, University of Wyoming, 82071, Laramie, WY, USA aut Journal of Molecular Evolution Springer-Verlag 73/1-2(2011-08-01), 23-33 0022-2844 73:1-2<23 2011 73 239 https://doi.org/10.1007/s00239-011-9454-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00239-011-9454-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Grahnen Johan Department of Molecular Biology, University of Wyoming, 82071, Laramie, WY, USA aut NATIONALLICENCE 700 1- Kubelka Jan Department of Chemistry, University of Wyoming, 82071, Laramie, WY, USA aut NATIONALLICENCE 700 1- Liberles David Department of Molecular Biology, University of Wyoming, 82071, Laramie, WY, USA aut NATIONALLICENCE 773 0- Journal of Molecular Evolution Springer-Verlag 73/1-2(2011-08-01), 23-33 0022-2844 73:1-2<23 2011 73 239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer