Model of the external force field for the protein folding process—the role of prefoldin

Abstract

Introduction: The protein folding process is very sensitive to environmental conditions. Many possibilities in the form of numerous pathways for this process can—if an incorrect one is chosen—lead to the creation of forms described as misfolded. The aqueous environment is the natural one for the protein folding process. Nonetheless, other factors such as the cell membrane and the presence of specific molecules (chaperones) affect this process, ensuring the correct expected structural form to guarantee biological activity. All these factors can be considered components of the external force field for this process.Methods: The fuzzy oil drop-modified (FOD-M) model makes possible the quantitative evaluation of the modification of the external field, treating the aqueous environment as a reference. The FOD-M model (tested on membrane proteins) includes the component modifying the water environment, allowing the assessment of the external force field generated by prefoldin.Results: In this work, prefoldin was treated as the provider of a specific external force field for actin and tubulin. The discussed model can be applied to any folding process simulation, taking into account the changed external conditions. Hence, it can help simulate the in silico protein folding process under defined external conditions determined by the respective external force field. In this work, the structures of prefoldin and protein folded with the participation of prefoldin were analyzed.Discussion: Thus, the role of prefoldin can be treated as a provider of an external field comparable to other environmental factors affecting the protein folding process.

External Force Field for Protein Folding in Chaperonins─Potential Application in In Silico Protein Folding

“…The specificity of protein structuring (folding in the presence and with the participation of chaperonins) is an example of the effect of the external force-field presence, which produces a final protein structure status that is far from the micelle-like arrangement . The example discussed represents a component of a certain set of proteins (prefoldin, chaperone) that provide a specific external force field, which, by active participation, affects the structuring of the final form of the protein. The evaluation and classification of these diverse external force fields also apply to the aqueous environment (that provides structuring with the micelle-like arrangement) and the hydrophobic environment of the cell membrane. – …”

“…Large complexes comprise numerous chains (often >10) that form a dual-ringed tetradecamer with the CN axis of symmetry, where the C -axis symmetry is the axis that passes through the axis of the capsid, and N denotes the number of chains in one-half of the capsid. These proteins can also participate in transport as done by prefoldin . GroEL promotes folding inside the capsid.…”

“…These proteins can also participate in transport as done by prefoldin. 3 GroEL promotes folding inside the capsid. This process requires energy (ATP) and proceeds with a temporarily significant change in the ordered symmetrical structure of GroEL.…”