1993
DOI: 10.1016/s0006-3495(93)81288-8
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Differential stability of beta-sheets and alpha-helices in beta-lactamase: a high temperature molecular dynamics study of unfolding intermediates

Abstract: beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypical of large alpha/beta proteins with a scaffolding formed by strong noncovalent interactions. Experimentally, the enzyme is well characterized, and intermediates that are slightly less compact and having nearly the same content of secondary structure have been identified in the folding pathway. In the present study, high temperature molecular dynamics simulations have been carried out on the native enzyme in solution. Analysis of these resul… Show more

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Cited by 44 publications
(34 citation statements)
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“…[11] There is ample evidence in the literature that several strains of b-lactamase follow a four-state unfolding mechanism. [18][19][20] It has been previously established by use of guanidinium chloride denaturation experiments that TEM-1 b-lactamase does not follow a simple "one-step, two-state" folding mechanism, but rather exhibits a thermodynamically stable intermediate state in equilibrium with the native and unfolded states, likely influenced by the cis/trans isomerization of XaaÀPro peptide bonds. [21] This intermediate state, described in the literature, is modeled here to correspond to the molten globule state of the four-state model.…”
Section: Comparison Of Models To Experimental Datamentioning
confidence: 99%
“…[11] There is ample evidence in the literature that several strains of b-lactamase follow a four-state unfolding mechanism. [18][19][20] It has been previously established by use of guanidinium chloride denaturation experiments that TEM-1 b-lactamase does not follow a simple "one-step, two-state" folding mechanism, but rather exhibits a thermodynamically stable intermediate state in equilibrium with the native and unfolded states, likely influenced by the cis/trans isomerization of XaaÀPro peptide bonds. [21] This intermediate state, described in the literature, is modeled here to correspond to the molten globule state of the four-state model.…”
Section: Comparison Of Models To Experimental Datamentioning
confidence: 99%
“…Further, the pathways of folding and unfolding have been shown to be similar and independent of temperature (6). Although folding has been investigated in many peptides and small proteins, only a few proteins of reasonably large size, such as hen egg-white lysozyme (7)(8)(9), dihydrofolatereductase (10), and b-lactamase (11), have been investigated for unfolding at high temperatures.…”
Section: Introductionmentioning
confidence: 99%
“…Monitoring the process of folding/unfolding is also a challenging task. The changes in parameters such as secondary structures (helices and sheets), native contacts, root meansquare deviation (RMSD), and radius of gyration are generally some of the important ones measured in following the folding/unfolding process (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, there is no systematic way to monitor the interactions of side chains in a collective manner, which is crucial for the intactness of the 3-D structure of a protein.…”
Section: Introductionmentioning
confidence: 99%
“…Previous simulation studies of protein folding fall into two types, namely reduced atom procedures, sometimes on a lattice, and all-atom simulations (see [17] for latest review). The allatom simulations, typically using molecular dynamics of fully solvated proteins at elevated temperatures, have been used to study the unfolding of a number of proteins including apomyoglobin, x lactalbumin, lysozyme, B-lactase, barnase and bovine pancreas trypsin inhibitor [18][19][20][21][22][23]. Not only are very high temperatures (ZOO-400°C) required but also long simulations (500-1000 ps) with concomitant computer resources just to produce one model pathway.…”
mentioning
confidence: 99%