Environmental Conditions Influencing the Folding Process

Author(s): Irena Roterman, Mateusz Slupina, Leszek Konieczny

Protein structure prediction remains an unsolved problem despite the significant progress brought by AI. Methods are evolving through reference to the growing resources of protein structure databases. However, the mechanism of the protein folding process remains unrecognised. A model was proposed to explain the incompatibility of the predicted structure with the native one. The reason for this is the influence of the environment, which, in a differentiated manner, directs the folding process to a form appropriate for the environment's characteristics. This is demonstrated using the lactococcin protein as an example. The structure of this protein was proposed for the targeting that the polar water environment brings. The native structure of this protein appears to represent the reconstitution of a distinct external force field with a hydrophobic component absent. This protein is active in the periplasmic space. The effect of this different environment on the folding process and the resulting different final structure was revealed. The results obtained allow a quantitative assessment of the environment affecting the location of energy minima to be introduced into the funnel model. The individual differentiated energy minimum imaged in the funnel model were placed on a scale expressing the specificity of the local environment of the folding protein.