@article {2149,
	title = {Configurational entropy modulates the mechanical stability of protein GB1},
	journal = {Journal of Molecular Biology},
	volume = {379},
	number = {4},
	year = {2008},
	note = {ISI Document Delivery No.: 314NITimes Cited: 10Cited Reference Count: 39Li, Hongbin Wang, Hui-Chuan Cao, Yi Sharma, Deepak Wang, Meijia},
	month = {Jun},
	pages = {871-880},
	type = {Article},
	abstract = {Configurational entropy plays important roles in defining the thermodynamic stability as well as the folding/unfolding kinetics of proteins. Here we combine single-molecule atomic force microscopy and protein engineering techniques to directly examine the role of configurational entropy in the mechanical unfolding kinetics and mechanical stability of proteins. We used a small protein, GB1, as a model system and constructed four mutants that elongate loop 2 of GB1 by 2, 5, 24 and 46 flexible residues, respectively. These loop elongation mutants fold properly as determined by far-UV circular dichroism spectroscopy, suggesting that loop 2 is well tolerant of loop insertions without affecting GB1{\textquoteright}s native structure. Our single-molecule atomic force microscopy results reveal that loop elongation decreases the mechanical stability of GB1 and accelerates the mechanical unfolding kinetics. These results can be explained by the loss of configurational entropy upon closing an unstructured flexible loop using classical polymer theory, highlighting the important role of loop regions in the mechanical unfolding of proteins. This study not only demonstrates a general approach to investigating the structural deformation of the loop regions in mechanical unfolding transition state, but also provides the foundation to use configurational entropy as an effective means to modulate the mechanical stability of proteins, which is of critical importance towards engineering artificial elastomeric proteins with tailored nanomechanical properties. (C) 2008 Elsevier Ltd. All rights reserved.},
	keywords = {configurational entropy, DISULFIDE BONDS, FORCE, FORCE SPECTROSCOPY, FRAGMENT RECONSTITUTION, IMMUNOGLOBULIN BINDING DOMAIN, length, LOOP, MECHANICAL STABILITY, mechanical unfolding, MODULES, resistance, single molecule atomic force microscopy, SINGLE PROTEIN, SPECTROSCOPY, TITIN, TRANSITION-STATE},
	isbn = {0022-2836},
	url = {<Go to ISI>://000256815700018},
	author = {Li, H. B. and Wang, H. C. and Cao, Y. and Sharma, D. and Wang, M.}
}
@article {1350,
	title = {Single molecule force spectroscopy reveals a weakly populated microstate of the FnIII domains of tenascin},
	journal = {Journal of Molecular Biology},
	volume = {361},
	number = {2},
	year = {2006},
	note = {ISI Document Delivery No.: 074WPTimes Cited: 8Cited Reference Count: 48Cao, Y. Li, Hongbin},
	month = {Aug},
	pages = {372-381},
	type = {Article},
	abstract = {The native states of proteins exist as an ensemble of conformationally similar microstates. The fluctuations among different microstates are of great importance for the functions and structural stability of proteins. Here, we demonstrate that single molecule atomic force microscopy (AFM) can be used to directly probe the existence of multiple folded microstates. We used the AFM to repeatedly stretch and relax a recombinant tenascin fragment TNfnALL to allow the fibronectin type III (FnIII) domains to undergo repeated unfolding/refolding cycles. In addition to the native state, we discovered that some FnIII domains can refold from the unfolded state into a previously unrecognized microstate, N* state. This novel state is conformationally similar to the native state, but mechanically less stable. The native state unfolds at similar to 120 pN, while the N* state unfolds at similar to 50 pN. These two distinct populations of microstates constitute the ensemble of the folded states for some FnIII domains. An unfolded FnIII domain can fold into either one of the two microstates via two distinct folding routes. These results reveal the dynamic and heterogeneous picture of the folded ensemble for some FnIII domains of tenascin, which may carry important implications for the mechanical functions of tenascins in vivo. (c) 2006 Elsevier Ltd. All rights reserved.},
	keywords = {DYNAMICS, fluctuations, FnIII domains, HYDROGEN-EXCHANGE, IMMUNOGLOBULIN, MECHANICAL STABILITY, mechanical unfolding, microscopy, MODULES, PROTEIN-STRUCTURE, scanning probe, single-molecule force spectroscopy, tenascin, TITIN, UNFOLDING PATHWAYS},
	isbn = {0022-2836},
	url = {<Go to ISI>://000239842800014},
	author = {Cao, Y. and Li, H. B.}
}
