The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function

Banach, Mateusz; Konieczny, Leszek; Roterman, Irena

doi:10.1016/j.jtbi.2014.05.007

Cited by 35 publications

(39 citation statements)

References 44 publications

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“…A similar relation between the hydrophobic core status and the amyloidogenic properties of transthyretin (1DVQ) is presented in [33]. Experiments have revealed significant differentiation of its N-and C-terminal halves, and the fuzzy oil drop model confirms functional differences between these sections [33].…”

Section: Determining the Biological Properties Of Proteins Based On Tmentioning

confidence: 71%

“…The parameters based on FOD calculated for different scales differ but the overall status of the molecule remains the same for all analyzed proteins. In conclusion, the choice of intrinsic hydrophobicity scale [31][32][33][34][35][36][37][38][39][40][41] does not appear to affect the outcome of fuzzy oil drop analysis. The comparative analysis was performed for hydrophobic parameters applying the KyteDoolittle scale [35] and shown in appropriate tables.…”

Section: The Real Hydrophobic Distribution In a Protein Moleculementioning

confidence: 85%

“…It can also be used to identify the location of ligand binding cavities [27,28], protein complexation areas [29,30], the structure of large protein complexes (such as chaperonin) [31] and the properties of proteins which include intrinsically disordered fragments [32] or share certain structural characteristics (e.g., immunoglobulin-like domains) [33]. In this work we apply the model to a set of relatively small proteins whose biological function involves interaction with DNA via a specific loop.…”

Section: Introductionmentioning

confidence: 99%

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Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins

Kalinowska

Banach

Konieczny

et al. 2015

Entropy

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Abstract:The fuzzy oil drop model, a tool which can be used to study the structure of the hydrophobic core in proteins, has been applied in the analysis of proteins belonging to the jumonji group-JARID2, JARID1A, JARID1B and JARID1D-proteins that share the property of being able to interact with DNA. Their ARID and PHD domains, when analyzed in the context of the fuzzy oil drop model, are found to exhibit structural variability regarding the status of their secondary folds, including the β-hairpin which determines their biological function. Additionally, the structure of disordered fragments which are present in jumonji proteins (as confirmed by the DisProt database) is explained on the grounds of the hydrophobic core model, suggesting that such fragments contribute to tertiary structural stabilization. This conclusion is supported by divergence entropy measurements, expressing the degree of ordering in each protein's hydrophobic core.

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Section: Determining the Biological Properties Of Proteins Based On Tmentioning

confidence: 71%

Section: The Real Hydrophobic Distribution In a Protein Moleculementioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins

Kalinowska

Banach

Konieczny

et al. 2015

Entropy

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“…Such domains are present in all immunoglobulins (where they determine their function) but are also encountered in enzymes and transport proteins [8][9][10]. Immunoglobulins exhibit high structural similarity, adopting characteristic "sandwich" conformations with rather low sequence similarity.…”

Section: Introductionmentioning

confidence: 99%

“…Even among immunoglobulins domains the λ and κ sequences are identified. Of course, the diversity of proteins which are not immunoglobulins but which do contain immunoglobulin-like domains is even greater [10].…”

Section: Introductionmentioning

confidence: 99%

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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Can the jigsaw puzzle model of protein folding re‐assemble a hydrophobic core?

et al. 2022

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According to the "jigsaw puzzle" model of protein folding, the isomorphism between sequence and structure is substantially determined by the specific geometry of sidechain interactions, within the protein interior. In this work, we have attempted to predict the hydrophobic core of cyclophilin (LdCyp) from Leishmania donovani, utilizing a surface complementarity function, which selects for high goodness of fit between hydrophobic side-chain surfaces, rather in the manner of assembling a three-dimensional jigsaw puzzle. The computational core prediction method implemented here has been tried on two distinct scenarios, on the LdCyp polypeptide chain with native non-core residues and all core residues initially set to alanine, on a poly-glycine polypeptide chain. Molecular dynamics simulations appeared to indicate partial destabilization of the two designed sequences. However, experimental characterization of the designed sequences by circular dichroism (CD) spectroscopy and denaturant (GdmCl) induced unfolding, demonstrated disordered proteins. Stepwise reconstruction of the designed cores by cumulative sequential mutations identified the specific mutation (M122L) as primarily responsible for fold collapse and all design objectives were achieved upon rectifying this mutation. In summary, the study demonstrates regions of the core to contain highly specific (jigsaw puzzle-like) interactions sensitive to any perturbations and a predictive algorithm to identify such regions. A mutation within the core has been identified which exercises an inordinate influence on the global fold, reminiscent of metamorphic proteins.In addition, the computational procedure could predict substantial regions of the core (given main-chain coordinates) without any reference to non-core residues.

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The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function

Cited by 35 publications

References 44 publications

Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins

Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins

Structural Role of Hydrophobic Core in Proteins-Selected Examples

Can the jigsaw puzzle model of protein folding re‐assemble a hydrophobic core?

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