Internal force field in selected proteins

Ptak-Kaczor, Magdalena; Banach, Mateusz; Konieczny, Leszek; Roterman, Irena

doi:10.18388/abp.2019_2865

Cited by 2 publications

(4 citation statements)

References 47 publications

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“…In addition, each residue also carries the so-called observed hydrophobicity (O i ), which is dependent on its hydrophobic interactions with adjacent residues. Such interactions depend on the separation between residues and on their intrinsic hydrophobicity, which is defined according to the scale proposed in Reference [52].…”

Section: Fuzzy Oil Drop Model-protein Folding With Preferential Genermentioning

confidence: 99%

“…To make meaningful observations, another reference distribution is required. In our case, this second "boundary" distribution is called R and denotes a case where all residues carry identical hydrophobicity (which is similar to the distribution of electrostatic interactions in many proteins [52]). Accordingly, the value of Ri for each residue is 1/N, N being the number of residues in the chain.…”

Section: Fuzzy Oil Drop Model-protein Folding With Preferential Genermentioning

confidence: 99%

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Alternative Structures of α-Synuclein

et al. 2020

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The object of our analysis is the structure of alpha-synuclein (ASyn), which, under in vivo conditions, associates with presynaptic vesicles. Misfolding of ASyn is known to be implicated in Parkinson’s disease. The availability of structural information for both the micelle-bound and amyloid form of ASyn enables us to speculate on the specific mechanism of amyloid transformation. This analysis is all the more interesting given the fact that—Unlike in Aβ(1–42) amyloids—only the central fragment (30–100) of ASyn has a fibrillar structure, whereas, its N- and C-terminal fragments (1–30 and 100–140, respectively) are described as random coils. Our work addresses the following question: Can the ASyn chain—as well as the aforementioned individual fragments—adopt globular conformations? In order to provide an answer, we subjected the corresponding sequences to simulations carried out using Robetta and I-Tasser, both of which are regarded as accurate protein structure predictors. In addition, we also applied the fuzzy oil drop (FOD) model, which, in addition to optimizing the protein’s internal free energy, acknowledges the presence of an external force field contributed by the aqueous solvent. This field directs hydrophobic residues to congregate near the center of the protein body while exposing hydrophilic residues on its surface. Comparative analysis of the obtained models suggests that fragments which do not participate in forming the amyloid fibril (i.e., 1–30 and 100–140) can indeed attain globular conformations. We also explain the influence of mutations observed in vivo upon the susceptibility of ASyn to undergo amyloid transformation. In particular, the 30–100 fragment (which adopts a fibrillar structure in PDB) is not predicted to produce a centralized hydrophobic core by any of the applied toolkits (Robetta, I-Tasser, and FOD). This means that in order to minimize the entropically disadvantageous contact between hydrophobic residues and the polar solvent, ASyn adopts the form of a ribbonlike micelle (rather than a spherical one). In other words, the ribbonlike micelle represents a synergy between the conformational preferences of the protein chain and the influence of its environment.

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Section: Fuzzy Oil Drop Model-protein Folding With Preferential Genermentioning

confidence: 99%

Section: Fuzzy Oil Drop Model-protein Folding With Preferential Genermentioning

confidence: 99%

Alternative Structures of α-Synuclein

et al. 2020

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“…The need for any direction of these effects has not been identified. 72,73 The set of enzymes presented is limited to a few examples. Large-scale analysis is needed and will continue.…”

Section: Discussionmentioning

confidence: 99%

“…Optimization methods (e.g., in the process of protein structure prediction) turn out to be appropriate in this context. The need for any direction of these effects has not been identified. , …”

Section: Discussionmentioning

confidence: 99%

Hydrophobicity-Based Force Field In Enzymes

Roterman,

Konieczny,

Stapor

et al. 2024

ACS Omega

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The biocatalysis process takes place with the participation of enzymes, which, depending on the reaction carried out, require, apart from the appropriate arrangement of catalytic residues, an appropriate external force field. It is generated by the protein body. The relatively small size of the part directly involved in the process itself is supported by the presence of an often complex structure of the protein body, the purpose of which is to provide an appropriate local force field, eliminating the influence of water. Very often, the large size of the enzyme is an expression of the complex form of this field. In this paper, a comparative analysis of arbitrarily selected enzymes, representatives of different enzyme classes, was carried out, focusing on the measurement of the diversity of the force field provided by a given protein. This analysis was based on the fuzzy oil drop model (FOD) and its modified version (FOD-M), which takes into account the participation of nonaqueous external factors in shaping the structure and thus the force field within the protein. The degree and type of ordering of the hydrophobicity distribution in the protein molecule is the result of the influence of the environment but also the supplier of the local environment for a given process, including the catalysis process in particular. Determining the share of a nonaqueous environment is important due to the ubiquity of polar water, whose participation in processes with high specificity requires control. It can be assumed that some enzymes in their composition have a permanently built-in part, the role of which is reduced to that of a permanent chaperone. It provides a specific external force field needed for the process. The proposed model, generalized to other types of proteins, may also provide a form of recording the environment model for the simulation of the in silico protein folding process, taking into account the impact of its differentiation.

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Internal force field in selected proteins

Cited by 2 publications

References 47 publications

Alternative Structures of α-Synuclein

Alternative Structures of α-Synuclein

Hydrophobicity-Based Force Field In Enzymes

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