Action-at-a-distance interactions enhance protein binding affinity. Export

@article{dfg:blipcomm, abstract = {The identification of protein mutations that enhance binding affinity may be achieved by computational or experimental means, or by a combination of the two. Sources of affinity enhancement may include improvements to the net balance of binding interactions of residues forming intermolecular contacts at the binding interface, such as packing and hydrogen-bonding interactions. Here we identify noncontacting residues that make substantial contributions to binding affinity and that also provide opportunities for mutations that increase binding affinity of the TEM1 beta-lactamase (TEM1) to the beta-lactamase inhibitor protein (BLIP). A region of BLIP not on the direct TEM1-binding surface was identified for which changes in net charge result in particularly large increases in computed binding affinity. Some mutations to the region have previously been characterized, and our results are in good correspondence with this results of that study. In addition, we propose novel mutations to BLIP that were computed to improve binding significantly without contacting TEM1 directly. This class of noncontacting electrostatic interactions could have general utility in the design and tuning of binding interactions.}, author = {Joughin, B. A. and Green, D. F. and Tidor, B.}, citeulike-article-id = {3859016}, citeulike-linkout-0 = {http://dx.doi.org/10.1110/ps.041283105}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15802650}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15802650}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/121602773/ABSTRACT}, doi = {10.1110/ps.041283105}, issn = {0961-8368}, journal = {Protein science : a publication of the Protein Society}, keywords = {action-at-a-distance, binding, electrostatics, protein}, month = {May}, number = {5}, pages = {1363--1369}, posted-at = {2009-01-07 23:19:09}, priority = {0}, title = {Action-at-a-distance interactions enhance protein binding affinity.}, url = {http://dx.doi.org/10.1110/ps.041283105}, volume = {14}, year = {2005} }

TY - JOUR ID - dfg:blipcomm L3 - citeulike-article-id:3859016 N2 - The identification of protein mutations that enhance binding affinity may be achieved by computational or experimental means, or by a combination of the two. Sources of affinity enhancement may include improvements to the net balance of binding interactions of residues forming intermolecular contacts at the binding interface, such as packing and hydrogen-bonding interactions. Here we identify noncontacting residues that make substantial contributions to binding affinity and that also provide opportunities for mutations that increase binding affinity of the TEM1 beta-lactamase (TEM1) to the beta-lactamase inhibitor protein (BLIP). A region of BLIP not on the direct TEM1-binding surface was identified for which changes in net charge result in particularly large increases in computed binding affinity. Some mutations to the region have previously been characterized, and our results are in good correspondence with this results of that study. In addition, we propose novel mutations to BLIP that were computed to improve binding significantly without contacting TEM1 directly. This class of noncontacting electrostatic interactions could have general utility in the design and tuning of binding interactions. IS - 5 JF - Protein science : a publication of the Protein Society SN - 0961-8368 EP - 1369 TI - Action-at-a-distance interactions enhance protein binding affinity. VL - 14 SP - 1363 KW - action-at-a-distance KW - binding KW - electrostatics KW - protein AU - Joughin, BA AU - Green, DF AU - Tidor, B PY - 2005/05// UR - http://dx.doi.org/10.1110/ps.041283105 ER -