“Fuzzy oil drop” model applied to individual small proteins built of 70 amino acids

Prymula, Katarzyna; Sałapa, Kinga; Roterman, Irena

doi:10.1007/s00894-009-0639-2

Cited by 7 publications

(8 citation statements)

References 65 publications

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“…In such a large complex, proteins that are recognized to fold in accordance with the ''fuzzy oil drop'' model may contribute to the environment for chains that fold later on (as is the case with hemoglobin, Brylinski et al, 2007b). Antifreeze proteins are structurally accordant with the presented model (Prymula et al, 2010). Similarly, chaperonins are good examples of the applicability of the presented model to large-scale structural analysis-in fact, some of them have already been recognized as supporting the reliability of the model (Prymula et al, 2009).…”

Section: Discussionmentioning

confidence: 53%

Two-intermediate model to characterize the structure of fast-folding proteins

Roterman

Konieczny

Jurkowski

et al. 2011

Journal of Theoretical Biology

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This paper introduces a new model that enables researchers to conduct protein folding simulations. A two-step in silico process is used in the course of structural analysis of a set of fast-folding proteins. The model assumes an early stage (ES) that depends solely on the backbone conformation, as described by its geometrical properties--specifically, by the V-angle between two sequential peptide bond planes (which determines the radius of curvature, also called R-radius, according to a second-degree polynomial form). The agreement between the structure under consideration and the assumed model is measured in terms of the magnitude of dispersion of both parameters with respect to idealized values. The second step, called late-stage folding (LS), is based on the "fuzzy oil drop" model, which involves an external hydrophobic force field described by a three-dimensional Gauss function. The degree of conformance between the structure under consideration and its idealized model is expressed quantitatively by means of the Kullback-Leibler entropy, which is a measure of disparity between the observed and expected hydrophobicity distributions. A set of proteins, representative of the fast-folding group - specifically, cold shock proteins - is shown to agree with the proposed model.

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Section: Discussionmentioning

confidence: 53%

Two-intermediate model to characterize the structure of fast-folding proteins

Roterman

Konieczny

Jurkowski

et al. 2011

Journal of Theoretical Biology

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“…When used for mutants it may estimate the influence of mutation on the potential loss of biological activity [22]. The position of mutation and its relation to the location of residues engaged in biological function may easily be visualized when the profile is presented ( expresses the difference between expected and observed hydrophobicity revealing the residues of significant difference between observation and the model).…”

Section: Discussionmentioning

confidence: 99%

Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants

et al. 2011

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Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with “fuzzy oil drop” model was selected for analysis.

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“…The applicability of FOD was tested on few selected sets of proteins of small size [38], structural similarity [39], protein complexes [40] and intrinsically disordered proteins [41].…”

Section: Discussionmentioning

confidence: 99%

“…This molecule also contains a loop (38)(39)(40)(41). The β-fragment at 42-46 and the loop both diverge from the model even though in G A 88 the same residues form parts of an accordant helix.…”

Section: De Novo Designed Proteinsmentioning

confidence: 91%

Structural Role of Hydrophobic Core in Proteins-Selected Examples

Banach¹,

Kalinowska²,

Konieczny³

et al. 2016

J Proteomics Bioinform

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This paper discusses the sequence/structure relation. The core question concerns the degree to which similar sequences produce similar structures and vice versa. A mechanism by which similar sequences may result in dissimilar structures is proposed, based on the Fuzzy Oil Drop (FOD) model in which structural similarity is estimated by analyzing the protein's hydrophobic core. We show that local changes in amino acid sequences, in addition to producing local structural alterations at the substitution site, may also change the shape of the hydrophobic core, significantly affecting the overall tertiary conformation of the protein. Our analysis focuses on four sets of proteins: 1) Pair of designer proteins with specially prepared sequences; 2) Pair of natural proteins modified (mutated) to converge to a point of high-level sequence identity while retaining their respective wild-type tertiary folds; 3) Pair of natural proteins with common ancestry but with differing structures and biological profiles shaped by divergent evolution; and 4) Pair of natural proteins of high structural similarity with no sequence similarity and different biological function. with even higher levels of sequence identity (95%) and differing folds. Thus, conformational switching to an alternative monomeric fold of comparable stability can be effected with just a handful of mutations in a small protein. This result has implications for understanding not only the folding code but also the evolution of new folds. The CATH [18] classification for these two proteins is as follows: 1.10.8.40-Mainly Alpha Orthogonal Bundle for 2JWS and 3.10.20.10.-R-Alpha Beta Roll for 2JWU. Wild type proteins with aim-oriented mutationsTwo proteins: G311 (1ZXG) and A219 (1ZXH) are modified versions of wild-type proteins designated G and A (IgG binding domains, source: Staphylococcus aureus for 1ZXG and Streptococcus sp. for 1ZXH) respectively [19]. The series of mutations aimed at achieving a high level of sequence identity while preserving wild-type 3D structures. Both proteins (G311 vs. G and A219 vs. A) represent backbone RMS-D 1.4 Å, maintaining wild-type secondary structures: α/β for G311 and helical for A219. The final sequence identity of both modified proteins is on the level of 59%. All relevant data was taken from a paper describing experimental results of protein modifications [19]. Homologous proteinsThe next pair comprises two proteins with common ancestry but different folds and functions: 2PIJ (Pfl 6 BETA) (source: Pseudomonas fluorescens) Cro protein from prophage pfl 6 in P. fluorescens pf-5 [20] and 3BD1 (Xfaso 1) Cro protein from putative prophage element X. fastidiosa strain ann-1 [20] (source: Xylella fastidiosa). Both proteins share an identical CATH classification: 1.10.260.40-Mainly Alpha Orthogonal Bundle.The differences between homologous proteins are due to evolutionary pressure. In the presented case the sequence identity is 40%, yet the α-helix is replaced by a β-sheet in the C-terminal region spanning approximately 25 residu...

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“Fuzzy oil drop” model applied to individual small proteins built of 70 amino acids

Cited by 7 publications

References 65 publications

Two-intermediate model to characterize the structure of fast-folding proteins

Two-intermediate model to characterize the structure of fast-folding proteins

Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants

Structural Role of Hydrophobic Core in Proteins-Selected Examples

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