Brylinski Michal, Konieczny Leszek, Roterman Irena
Department of Bioinformatics and Telemedicine, Collegium Medicum--Jagiellonian University, Kopernika 17, 31-501 Krakow, Poland.
J Biomol Struct Dyn. 2006 Apr;23(5):519-28. doi: 10.1080/07391102.2006.10507076.
A model of hydrophobic collapse (in silico), which is generally considered to be the driving force for protein folding, is presented in this work. The model introduces the external field in the form of a fuzzy-oil-drop assumed to represent the environment. The drop is expressed in the form of a three-dimensional Gauss function. The usual probability value is assumed to represent the hydrophobicity distribution in the three-dimensional space of the virtual environment. The differences between this idealized hydrophobicity distribution and the one represented by the folded polypeptide chain is the parameter to be minimized in the structure optimization procedure. The size of fuzzy-oil-drop is critical for the folding process. A strong correlation between protein length and the dimension of the native and early-stage molecular form was found on the basis of single-domain proteins analysis. A previously presented early-stage folding (in silico) model was used to create the starting structure for the procedure of late-stage folding of lysozyme. The results of simulation were found to be promising, although additional improvements for the formation of beta-structure and disulfide bonds as well as the participation of natural ligand in folding process seem to be necessary.
本文提出了一种疏水塌缩模型（计算机模拟），该模型通常被认为是蛋白质折叠的驱动力。该模型以假定代表环境的模糊油滴形式引入外部场。该油滴以三维高斯函数的形式表示。假定通常的概率值代表虚拟环境三维空间中的疏水性分布。这种理想化的疏水性分布与折叠多肽链所代表的疏水性分布之间的差异是结构优化过程中要最小化的参数。模糊油滴的大小对折叠过程至关重要。基于单结构域蛋白质分析，发现蛋白质长度与天然和早期分子形式的尺寸之间存在很强的相关性。使用先前提出的早期折叠（计算机模拟）模型为溶菌酶后期折叠过程创建起始结构。模拟结果很有前景，尽管似乎有必要对β结构和二硫键的形成以及天然配体在折叠过程中的参与进行进一步改进。
