Modeling of protein binary complexes using structural mass spectrometry data

@article{citeulike:2158190, abstract = {In this article, we describe a general approach to modeling the structure of binary protein complexes using structural mass spectrometry data combined with molecular docking. In the first step, hydroxyl radical mediated oxidative protein footprinting is used to identify residues that experience conformational reorganization due to binding or participate in the binding interface. In the second step, a three-dimensional atomic structure of the complex is derived by computational modeling. Homology modeling approaches are used to define the structures of the individual proteins if footprinting detects significant conformational reorganization as a function of complex formation. A three-dimensional model of the complex is constructed from these binary partners using the ClusPro program, which is composed of docking, energy filtering, and clustering steps. Footprinting data are used to incorporate constraintspositive and/or negativein the docking step and are also used to decide the type of energy filterelectrostatics or desolvationin the successive energy-filtering step. By using this approach, we examine the structure of a number of binary complexes of monomeric actin and compare the results to crystallographic data. Based on docking alone, a number of competing models with widely varying structures are observed, one of which is likely to agree with crystallographic data. When the docking steps are guided by footprinting data, accurate models emerge as top scoring. We demonstrate this method with the actin/gelsolin segment-1 complex. We also provide a structural model for the actin/cofilin complex using this approach which does not have a crystal or NMR structure. 10.1110/ps.073071808}, author = {Kamal, Amisha J. K. and Chance, Mark R. }, citeulike-article-id = {2158190}, doi = {10.1110/ps.073071808}, journal = {Protein Sci}, keywords = {complex, massspectrometry, protein, structure}, month = {January}, number = {1}, pages = {79--94}, posted-at = {2007-12-22 03:02:36}, priority = {4}, title = {Modeling of protein binary complexes using structural mass spectrometry data}, url = {http://dx.doi.org/10.1110/ps.073071808}, volume = {17}, year = {2008} }

TY - JOUR ID - citeulike:2158190 L3 - citeulike-article-id:2158190 TI - Modeling of protein binary complexes using structural mass spectrometry data JF - Protein Sci VL - 17 IS - 1 SP - 79 EP - 94 N2 - In this article, we describe a general approach to modeling the structure of binary protein complexes using structural mass spectrometry data combined with molecular docking. In the first step, hydroxyl radical mediated oxidative protein footprinting is used to identify residues that experience conformational reorganization due to binding or participate in the binding interface. In the second step, a three-dimensional atomic structure of the complex is derived by computational modeling. Homology modeling approaches are used to define the structures of the individual proteins if footprinting detects significant conformational reorganization as a function of complex formation. A three-dimensional model of the complex is constructed from these binary partners using the ClusPro program, which is composed of docking, energy filtering, and clustering steps. Footprinting data are used to incorporate constraintspositive and/or negativein the docking step and are also used to decide the type of energy filterelectrostatics or desolvationin the successive energy-filtering step. By using this approach, we examine the structure of a number of binary complexes of monomeric actin and compare the results to crystallographic data. Based on docking alone, a number of competing models with widely varying structures are observed, one of which is likely to agree with crystallographic data. When the docking steps are guided by footprinting data, accurate models emerge as top scoring. We demonstrate this method with the actin/gelsolin segment-1 complex. We also provide a structural model for the actin/cofilin complex using this approach which does not have a crystal or NMR structure. 10.1110/ps.073071808 KW - complex KW - massspectrometry KW - protein KW - structure AU - Kamal, Amisha AU - Chance, Mark PY - 2008/01/01/ UR - http://dx.doi.org/10.1110/ps.073071808 ER -