skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Contact order revisited: Influence of protein size on the folding rate

Abstract

Guided by the recent success of empirical model predicting the folding rates of small two-state folding proteins from the relative contact order (CO) of their native structures, by a theoretical model of protein folding that predicts that logarithm of the folding rate decreases with the protein chain length L as L2/3, and by the finding that the folding rates of multistate folding proteins strongly correlate with their sizes and have very bad correlation with CO, we reexamined the dependence of folding rate on CO and L in attempt to find a structural parameter that determines folding rates for the totality of proteins. We show that the Abs{sub CO} = CO x L, is able to predict rather accurately folding rates for both two-state and multistate folding proteins, as well as short peptides, and that this Abs{sub CO} scales with the protein chain length as L0.70 {+-} 0.07 for the totality of studied single-domain proteins and peptides.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Director. Office of Science. Office of Biological and Environmental Research (US)
OSTI Identifier:
827973
Report Number(s):
LBNL-56029
R&D Project: VGTLAA; TRN: US200426%%1033
DOE Contract Number:
AC03-76SF00098
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein Science; Journal Volume: 12; Other Information: Journal Publication Date: June 2003; PBD: 28 May 2003
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; PEPTIDES; PROTEINS; LAWRENCE BERKELEY LABORATORY; PROTEIN FOLDING KINETICS TWO-STATE KINETICS MULTISTATE KINETICS CONTACT ORDER PROTEIN SIZE PROTEIN TOPOLOGY RATE OF FOLDIN

Citation Formats

Ivankov, Dmitry N., Garbuzynskiy, Sergiy O., Alm, Eric, Plaxco, Kevin W., Baker, David, and Finkelstein, Alexei V. Contact order revisited: Influence of protein size on the folding rate. United States: N. p., 2003. Web. doi:10.1110/ps.0302503.
Ivankov, Dmitry N., Garbuzynskiy, Sergiy O., Alm, Eric, Plaxco, Kevin W., Baker, David, & Finkelstein, Alexei V. Contact order revisited: Influence of protein size on the folding rate. United States. doi:10.1110/ps.0302503.
Ivankov, Dmitry N., Garbuzynskiy, Sergiy O., Alm, Eric, Plaxco, Kevin W., Baker, David, and Finkelstein, Alexei V. Wed . "Contact order revisited: Influence of protein size on the folding rate". United States. doi:10.1110/ps.0302503.
@article{osti_827973,
title = {Contact order revisited: Influence of protein size on the folding rate},
author = {Ivankov, Dmitry N. and Garbuzynskiy, Sergiy O. and Alm, Eric and Plaxco, Kevin W. and Baker, David and Finkelstein, Alexei V.},
abstractNote = {Guided by the recent success of empirical model predicting the folding rates of small two-state folding proteins from the relative contact order (CO) of their native structures, by a theoretical model of protein folding that predicts that logarithm of the folding rate decreases with the protein chain length L as L2/3, and by the finding that the folding rates of multistate folding proteins strongly correlate with their sizes and have very bad correlation with CO, we reexamined the dependence of folding rate on CO and L in attempt to find a structural parameter that determines folding rates for the totality of proteins. We show that the Abs{sub CO} = CO x L, is able to predict rather accurately folding rates for both two-state and multistate folding proteins, as well as short peptides, and that this Abs{sub CO} scales with the protein chain length as L0.70 {+-} 0.07 for the totality of studied single-domain proteins and peptides.},
doi = {10.1110/ps.0302503},
journal = {Protein Science},
number = ,
volume = 12,
place = {United States},
year = {Wed May 28 00:00:00 EDT 2003},
month = {Wed May 28 00:00:00 EDT 2003}
}
  • No abstract prepared.
  • The contribution of a pair of functional groups that can form either intermolecular or intramolecular hydrogen bonds to the total standard free energy of the process of protein folding or protein association is examined. It is found that this contribution can be quite large, either positive or negative, depending on the particular process and on the solvent density. This is in contrast to the common belief that the hydrogen-bond energies tend to be compensated in these processes. For the binding process, in which the two functional groups are completely removed from the aqueous environment, the contribution of such a pairmore » of functional groups to {Delta}G can be as high as +6.4 kcal/mol. This is the main reason why hydrophobic rather than hydrophilic surfaces tend to attach to each other. In contrast, when the two functional groups are only partially removed from the aqueous environment, as in the case of the formation of {alpha}-helix, their contribution to {Delta}G can be negative and of the order of about 1 kcal/mol.« less
  • Studies of the native structures of proteins, together with measurements of the thermodynamic properties of the transition between unfolded and native states, have defined the major compon tructuresents of the forces that stabilize native protein structures. However, the nature of the intermediates in the folding process remains largely hypothetical. We wished to examine what happens if, during the folding of a monomeric protein, regions of secondary structure come together to form an intermediate of reduced instability. We applied calculations of accessible surface area and parameterized nonbonded energy calculations to identify the kinds of stabilizing interactions that might be available tomore » such an intermediate. First, we analyzed the total buried surface area of two types of proteins into contributions from formation of secondary structure alone, interaction of pairs of secondary-structural elements, the formation of the complete secondary structure without the turns, and the complete native structure. We then analyzed in more detail the approach of two ..cap alpha..-helices to form a complex, as an illustrative example of the nature of the interaction between compact structural units which remain fairly rigid during their interaction. The computational experiments we have performed were an attempt to describe how certain components of the interaction energy vary with the relative position and orientation of the interacting units. Although we used the best numerical estimates of the energy components that were available to us, the qualitative features of our results do not depend on the precision of the parameters.« less
  • The dynamics and energetics of formation of loops in the 46-residue N-terminal fragment of the B-domain of staphylococcal protein A has been studied. Numerical simulations have been performed using coarse-grained molecular dynamics with the united-residue (UNRES) force field. The results have been analyzed in terms of a kink (heteroclinic standing wave solution) of a generalized discrete nonlinear Schrödinger (DNLS) equation. In the case of proteins, the DNLS equation arises from a C{sup α}-trace-based energy function. Three individual kink profiles were identified in the experimental three-α-helix structure of protein A, in the range of the Glu16-Asn29, Leu20-Asn29, and Gln33-Asn44 residues, respectively;more » these correspond to two loops in the native structure. UNRES simulations were started from the full right-handed α-helix to obtain a clear picture of kink formation, which would otherwise be blurred by helix formation. All three kinks emerged during coarse-grained simulations. It was found that the formation of each is accompanied by a local free energy increase; this is expressed as the change of UNRES energy which has the physical sense of the potential of mean force of a polypeptide chain. The increase is about 7 kcal/mol. This value can thus be considered as the free energy barrier to kink formation in full α-helical segments of polypeptide chains. During the simulations, the kinks emerge, disappear, propagate, and annihilate each other many times. It was found that the formation of a kink is initiated by an abrupt change in the orientation of a pair of consecutive side chains in the loop region. This resembles the formation of a Bloch wall along a spin chain, where the C{sup α} backbone corresponds to the chain, and the amino acid side chains are interpreted as the spin variables. This observation suggests that nearest-neighbor side chain–side chain interactions are responsible for initiation of loop formation. It was also found that the individual kinks are reflected as clear peaks in the principal modes of the analyzed trajectory of protein A, the shapes of which resemble the directional derivatives of the kinks along the chain. These observations suggest that the kinks of the DNLS equation determine the functionally important motions of proteins.« less
  • In earlier works, we showed that the entropic effect originating from the translational displacement of water molecules plays the pivotal role in protein folding and denaturation. The two different solvent models, hard-sphere solvent and model water, were employed in theoretical methods wherein the entropic effect was treated as an essential factor. However, there were similarities and differences in the results obtained from the two solvent models. In the present work, to unveil the physical origins of the similarities and differences, we simultaneously consider structural transition, cold denaturation, and pressure denaturation for the same protein by employing the two solvent modelsmore » and considering three different thermodynamic states for each solvent model. The solvent-entropy change upon protein folding/unfolding is decomposed into the protein-solvent pair (PA) and many-body (MB) correlation components using the integral equation theories. Each component is further decomposed into the excluded-volume (EV) and solvent-accessible surface (SAS) terms by applying the morphometric approach. The four physically insightful constituents, (PA, EV), (PA, SAS), (MB, EV), and (MB, SAS), are thus obtained. Moreover, (MB, SAS) is discussed by dividing it into two factors. This all-inclusive investigation leads to the following results: (1) the protein-water many-body correlation always plays critical roles in a variety of folding/unfolding processes; (2) the hard-sphere solvent model fails when it does not correctly reproduce the protein-water many-body correlation; (3) the hard-sphere solvent model becomes problematic when the dependence of the many-body correlation on the solvent number density and temperature is essential: it is not quite suited to studies on cold and pressure denaturating of a protein; (4) when the temperature and solvent number density are limited to the ambient values, the hard-sphere solvent model is usually successful; and (5) even at the ambient values, however, the many-body correlation plays significant roles in the β-sheet formation and argument of relative stabilities of very similar structures of a protein. These results are argued in detail with respect to the four physically insightful constituents and the two factors mentioned above. The relevance to the absence or presence of hydrogen-bonding properties in the solvent is also discussed in detail.« less