Roterman Irena, Slupina Mateusz, Konieczny Leszek
Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College, Medyczna 7, 30-688 Kraków, Poland.
Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków, Poland.
Comput Struct Biotechnol J. 2024 Oct 21;23:3827-3838. doi: 10.1016/j.csbj.2024.10.030. eCollection 2024 Dec.
The spatial structure of proteins, largely determined by their amino acid sequences, is also dependent on the environmental conditions under which the folding process takes place. In aqueous environments, exposure of polar amino acids is the driving factor, whereas protein stabilization in amphipathic membranes requires exposure to hydrophobic residues. This observation can be extended to all other environmental conditions under which proteins exhibit biological activity and, most importantly, to the folding process. The fuzzy oil drop (FOD) model assumes a centric location of hydrophobic residues (hydrophobic core) with exposure of polar residues towards the aqueous environment, as the influence of the aqueous environment is extended to include the contribution of other non-aqueous factors, enabling the assessment of their influence on protein structuring. The application of the modified FOD model (FOD-M) we have developed allows the environment to be represented as an external force field in the form of a continuum. The role of environmental conditions allows modification of the funnel model expressing the localization of the energy minimum as dependent on external conditions expressed by the K scale, where K measures the degree of other than polar water factors participating in folding process.
蛋白质的空间结构在很大程度上由其氨基酸序列决定，同时也取决于蛋白质折叠过程发生时的环境条件。在水性环境中，极性氨基酸的暴露是驱动因素，而在两亲性膜中蛋白质的稳定则需要暴露疏水残基。这一观察结果可以扩展到蛋白质表现出生物活性的所有其他环境条件，最重要的是，扩展到折叠过程。模糊油滴（FOD）模型假定疏水残基（疏水核心）位于中心位置，极性残基暴露于水性环境中，因为水性环境的影响被扩展到包括其他非水因素的贡献，从而能够评估它们对蛋白质结构的影响。我们开发的改进模糊油滴模型（FOD-M）的应用允许将环境表示为连续统形式的外力场。环境条件的作用使得能够修改漏斗模型，该模型将能量最小值的定位表示为取决于由K尺度表示的外部条件，其中K衡量参与折叠过程的除极性水因素之外的其他因素的程度。
