Diffusional Encounter of Barnase and Barstar Export

@article{citeulike:2328900, abstract = {We present an analysis of trajectories from Brownian dynamics simulations of diffusional protein-protein encounter for the well-studied system of barnase and barstar. This analysis reveals details about the optimal association pathways, the regions of the encounter complex, possible differences of the pathways for dissociation and association, the coupling of translational and rotation motion, and the effect of mutations on the trajectories. We found that a small free-energy barrier divides the energetically most favorable region into a region of the encounter complex above the barnase binding interface and a region around a second energy minimum near the RNA binding loop. When entering the region of the encounter complex from the region near the RNA binding loop, barstar has to change its orientation to increase the electrostatic attraction between the proteins. By concentrating the analysis on the successful binding trajectories, we found that the region of the second minimum is not essential for the binding of barstar to barnase. Nevertheless, this region may be helpful to steer barstar into the region of the encounter complex. When applying the same analysis to several barnase mutants, we found that single mutations may drastically change the free-energy landscape and may significantly alter the population of the two minima. Therefore, certain protein-protein pairs may require careful adaptation of the positions of encounter and transition states when interpreting mutation effects on kinetic rates of association and/or dissociation. 10.1529/biophysj.105.075507}, author = {Spaar, Alexander and Dammer, Christian and Gabdoulline, Razif R. and Wade, Rebecca C. and Helms, Volkhard}, citeulike-article-id = {2328900}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.105.075507}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0006349506723785}, citeulike-linkout-2 = {http://www.biophysj.org/cgi/content/abstract/90/6/1913}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/16361332}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=16361332}, day = {15}, doi = {10.1529/biophysj.105.075507}, journal = {Biophys. J.}, keywords = {bd\_simulation, clustering}, month = {March}, number = {6}, pages = {1913--1924}, posted-at = {2009-03-05 00:43:04}, priority = {2}, title = {Diffusional Encounter of Barnase and Barstar}, url = {http://dx.doi.org/10.1529/biophysj.105.075507}, volume = {90}, year = {2006} }

TY - JOUR ID - citeulike:2328900 L3 - citeulike-article-id:2328900 N2 - We present an analysis of trajectories from Brownian dynamics simulations of diffusional protein-protein encounter for the well-studied system of barnase and barstar. This analysis reveals details about the optimal association pathways, the regions of the encounter complex, possible differences of the pathways for dissociation and association, the coupling of translational and rotation motion, and the effect of mutations on the trajectories. We found that a small free-energy barrier divides the energetically most favorable region into a region of the encounter complex above the barnase binding interface and a region around a second energy minimum near the RNA binding loop. When entering the region of the encounter complex from the region near the RNA binding loop, barstar has to change its orientation to increase the electrostatic attraction between the proteins. By concentrating the analysis on the successful binding trajectories, we found that the region of the second minimum is not essential for the binding of barstar to barnase. Nevertheless, this region may be helpful to steer barstar into the region of the encounter complex. When applying the same analysis to several barnase mutants, we found that single mutations may drastically change the free-energy landscape and may significantly alter the population of the two minima. Therefore, certain protein-protein pairs may require careful adaptation of the positions of encounter and transition states when interpreting mutation effects on kinetic rates of association and/or dissociation. 10.1529/biophysj.105.075507 IS - 6 JF - Biophys. J. EP - 1924 TI - Diffusional Encounter of Barnase and Barstar VL - 90 SP - 1913 KW - bd_simulation KW - clustering AU - Spaar, Alexander AU - Dammer, Christian AU - Gabdoulline, Razif AU - Wade, Rebecca AU - Helms, Volkhard PY - 2006/03/15/ UR - http://dx.doi.org/10.1529/biophysj.105.075507 ER -