The models of the denaturation of globular proteins. I. Theory of globula–coil transitions in macromolecules

Ptitsyn, Oleg B.; Kron, A.K.; Éizner, Yu.Ye.

doi:10.1002/polc.5070160644

Cited by 104 publications

(70 citation statements)

References 12 publications

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“…In principle, for a description of the globular state one should also include the n-body interactions with n A 3. The number density of these interactions is in general negligible if the chain is viewed as a gas of disconnected monomers 33) . Their number is increased by chain connectivity that brings together clusters of topologically close monomers.…”

Section: X9mentioning

confidence: 99%

Polymer association in poor solvents: from monomolecular micelles to clusters of chains and phase separation

Raos

Allegra

1999

Macromol. Theory Simul.

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SUMMARY: We report some recent results obtained in our laboratory on the poor-solvent behavior of macromolecules. We first discuss the globular collapse of short chains that, unlike long ones, may form compact ordered states. We then address the collapse of random AB copolymers, which may provide significant clues to understanding biophysical issues such as the protein folding problem or the DNA arrangement in a living cell. Afterwards, we turn to the many-chain problem of homopolymer aggregation into polymolecular micelles or clusters of chains and eventually phase separation. The unifying feature of our approach consists in the self-consistent free-energy minimization with inclusion of intra-and inter-molecular interactions, whenever they are required, that enables us to describe the chain conformation in detail. General introductionThe collapse of a polymer chain to the globular state in poor solvents has received a wide interest both as a natural extension of the study of long-range a interactions beyond the good-solvent conditions 1,2) , and as a possible key to understand complex biophysical phenomena, in particular the native state of globular proteins or the conformation of DNA in a living cell 1) . Furthermore, it is a prerequisite for a description of coil aggregation leading to the formation of polymolecular micelles and eventually precipitation. While the general features of the collapse of long homopolymer chains (i. e., formed by identical repeat units) are relatively well understood 1, 3-7) , this is not so for short chains, in particular with reference to their local conformation. Most approaches are instead mainly focused on the overall features of the resulting globule. Therefore, in this Feature Article we discuss some recent theoretical results obtained in our laboratory on the poor-solvent behavior which stress the importance of the intramolecular degrees of freedom.Coil collapse is usually compared to the condensation of a vapor to the liquid phase. However, it was suggested 1, 3) that a slim chain may undergo other transitions to some "ordered" state, somehow akin to the formation of a crystal, or at least of a liquid crystal with nematic order. This indeed turns out to be the case for short chains 8) , as we shall report in the present paper. Also, the process of aggregation and precipitation confronts us with open issues, concerning for example the coil conformation near the critical point. Thus, we shall also address many-chain systems. Homopolymers are clearly a poor model for proteins, that may be regarded as copolymers with very specific monomer sequences (the aminoacid residues). Therefore, later efforts were directed to the study of appropriate copolymers [9][10][11][12][13][14][15][16] . For instance, simulation studies usually considered chains formed by unlike units, whereas other approaches took for simplicity AB copolymers consisting of hydrophobic and hydrophilic units only. Accordingly, we shall also report our recent work on the collapse of random copolymers formed by two di...

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Section: X9mentioning

confidence: 99%

Polymer association in poor solvents: from monomolecular micelles to clusters of chains and phase separation

Raos

Allegra

1999

Macromol. Theory Simul.

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“…[1][2][3] Below the LCST, the polymer is soluble due to the hydrogen bonds formed between the water molecules and the amide groups. The coil-globule transition at the LCST arises from breaking of the hydrogen bonds and from the expelling of water molecules, leading to polymer precipitation into particles and to a two-phase system.…”

Section: Introductionmentioning

confidence: 99%

Triggering the Thermosensitive Properties of Hydrophobically Modified Poly(N‐isopropylacrylamide) by Complexation with Cyclodextrin Polymers

Wintgens

Charles

Allouache

2005

Macro Chemistry & Physics

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Summary: Hydrophobically modified poly(N‐isopropylacrylamide) (PNIPAM) containing either an adamantyl or a dodecyl group were prepared and characterized. Self‐association in aqueous solutions was evidenced by fluorescence measurements using pyrene as a probe. The lower critical solution temperatures (LCST) were determined from cloud point measurements. They strongly depended on the hydrophobic group and the substitution level. The association between hydrophobically modified PNIPAM and β‐cyclodextrin (monomers and polymers) was investigated by cloud point and viscosity measurements. The presence of β‐cyclodextrin monomers generally shifted the LCST to a higher temperature, the complexation increasing the solubility of PNIPAM chains. β‐Cyclodextrin polymers mixed with hydrophobically modified PNIPAM generated supramolecular assemblies. This was evidenced by viscosity measurements of the mixtures at temperatures lower than the LCST. Moreover, depending on the substitution level of the PNIPAM, the LCST was increased (1% hydrophobic groups) or decreased (4% hydrophobic groups) by more than 10 °C upon β‐cyclodextrin polymer addition.

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“…This has been a matter of contention (Ptitsyn et al, 1968;de Gennes, 1975;Post & Zimm, 1979;Sanchez, 1979;Grosberg & Khokhlov, 1987). Although Ptitsyn et al (1968) argued that homopolymer collapse should be two-state in the limit of infinite chain length, it now appears that the collapse of a flexible homopolymer chain of finite length is a onestate transition (Sun et al, 1980;Tiktopulo et al, 1994), unless chain stiffness is high, as in DNA (de Gennes, 1975;Post & Zimm, 1979;reviewed by Chan & Dill, 1991a. In this regard the collapse of flexible homopolymers is less cooperative than the two-state folding attributed to small globular proteins.…”

Section: Protein Folding Cooperativity: a Simplest Hypothesismentioning

confidence: 99%

“…Homopolymers are predicted to collapse when they are put into "poor" solvents (i.e., solvents that prefer phase separation to mixing with monomers of the type that comprise the homopolymer) (Anufrieva et al, 1968;Ptitsyn et al, 1968;de Gennes, 1975;Post & Zimm, 1979;Sanchez, 1979;Williams et al, 1981). It is observed experimentally that polystyrene, a chain of nonpolar monomers, collapses to a compact globule in a poor organic solvent (Sun et al, 1980) and poly-(Nisopropylacrylamide) (PNIPAM) collapses very sharply (with increasing temperature) in water (Fujishige et al, 1989;RiEka et al, 1990;Meewes et al, 1991;Tiktopulo et al, 1994), resembling the renaturation of cold-denatured proteins (Privalov & Gill, 1988;see Fig.…”

Section: Nonlocal Interactions Drive Collapse Transitions Whereas Lomentioning

confidence: 99%

Principles of protein folding — A perspective from simple exact models

et al. 1995

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General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics-fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse.Keywords: chain collapse; hydrophobic interactions; lattice models; protein conformations; protein folding; protein stabilityWe review the principles of protein structure, stability, and folding kinetics from the perspective of simple exact models. We focus on the "folding code''-how the tertiary structure and folding pathway of a protein are encoded in its amino acid sequence. Although native proteins are specific, compact, and often remarkably symmetrical structures, ordinary synthetic polymers in solution, glasses, or melts adopt large ensembles of more expanded conformations, with little intrachain organization. With simple exact models, we ask what are the fundamental causes of the differences between proteins and other polymers-What makes proteins special?One view of protein folding assumes that the "local" interactions among the near neighbors in the amino acid sequence, the interactions that form helices and turns, are the main determinants of protein structure. This assumption implies that isolated helices form early in the protein folding pathway and then assemble into the native tertiary structure (see Fig. 1). It is the premise behind the paradigm, primary + secondary -+ tertiary structure, that seeks computer algorithms to predict secondary structures from the sequence, and then to assemble them into the tertiary native structure.Here we review a simple model of an alternative view, its basis in experimental results, and its implications. We show how the nonlocal interactions that drive collapse processes in heteropolymers can give rise to protein structure, stability, and folding kinetics. This perspective is based on evidence that the folding code is not predominantly localized in short windows of the amino acid sequence. It...

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The models of the denaturation of globular proteins. I. Theory of globula–coil transitions in macromolecules

Cited by 104 publications

References 12 publications

Polymer association in poor solvents: from monomolecular micelles to clusters of chains and phase separation

Polymer association in poor solvents: from monomolecular micelles to clusters of chains and phase separation

Triggering the Thermosensitive Properties of Hydrophobically Modified Poly(N‐isopropylacrylamide) by Complexation with Cyclodextrin Polymers

Principles of protein folding — A perspective from simple exact models

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