Fuzzy-oil-drop hydrophobic force field—a model to represent late-stage folding (in silico) of lysozyme

Michal Brylinski, Uniwersytet Jagielloński Collegium Medicum
Leszek Konieczny, Uniwersytet Jagielloński Collegium Medicum
Irena Roterman, Uniwersytet Jagielloński Collegium Medicum


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 β-structure and disulfide bonds as well as the participation of natural ligand in folding process seem to be necessary. © 2006 Taylor & Francis Group, LLC.