Elaboration of Simplest Folding Structures in 2-Dimensional Lattice with Delta-Hemolysin and Its Variants in HP Model

Shaomin Yan,Guang Wu

doi:10.4236/jbise.2019.125022

Abstract

Although the advanced 3-dimensional structure measurements provide more and more detailed structures in Protein Data Bank, the simplest 2-dimensional lattice model still looks meaningful because 2-dimensional structures play a complementary role with respect to 3-dimensional structures. In this study, the folding structures of delta-hemolysin and its six variants were studied at 2-dimensional lattice, and their amino acid contacts in folding structures were considered according to HP model with the aid of normalized amino acid hydrophobicity index. The results showed that: 1) either delta-hemolysin or each of its variants could find any of its folding structure in one eighth of 1,129,718,145,924 folding structures because of symmetry, which reduces the time required for folding, 2) the impact of pH on folding structures is varying and associated directly with the amino acid sequence itself, 3) the changes in folding structures of variants appeared different case by case, and 4) the assigning of hydrophobicity index to each amino acid was a way to distinguish folding structures at the same native state. This study can help to understand the structure of delta-hemolysin, and such an analysis can shed lights on NP-problem listed in millennium prize because the HP folding in lattice belongs to a sub-problem of NP-problem.

Highlights

With the advance of technologies in 3-dimensional structure measurements, more and more detailed structures are documented in Protein Data Bank [1, 2]
If those neutral amino acids are dealt properly, the HP model would work in real-life case, for which the normalized amino acid hydrophobicity index (Table 1), where only glycine is considered as a neutral amino acid [26]
The merit of HP model is to divide amino acids into hydrophobic (H) or polar (P), it is easy to find out the native state of folding structure with maximal H-H contacts, whereas it is quite laboring to find any amino acid contacts with respect to any combination of two amino acids

Summary

Introduction

With the advance of technologies in 3-dimensional structure measurements, more and more detailed structures are documented in Protein Data Bank [1, 2]. The simplest 2-dimensional lattice model looks more meaningful nowadays than before because: 1) 2-dimensional structures do not exist in reality and play a complementary role with respect to 3-dimensional structures; 2) the folding in 2-dimensional lattice tells the ways of how a protein folds since 3-dimensional data document only limited ways that a protein folds if any; 3) the ways that a protein folds provide a clue how a protein folds itself within a very tiny interval of time; 4) it is more efficient and effective to optimize computing algorithms in 2-dimensional lattice rather than in 3-dimensional lattice; 5) the computation of exhaustive folding structures would be a good measure of how the computing power advances; 6) models can tell us the future whereas data only record the past; and 7) our daily experience indicates that we are comfortable to have a family album rather than a collection of 3-dimensional statues of family members, i.e., 2-dimensional data are easier to store than 3-dimensional data. Studies of protein folding along 2-dimensional lattice should not be abandoned

Methods

Results

Conclusion