Probing the folding of mini-protein Beta3s by two-dimensional infrared spectroscopy; simulation study

Christopher Nj Marai,Jin Wang,Shaul Mukamel

doi:10.1186/1757-5036-3-8

Abstract

We propose to use infrared coherent two-dimensional correlation spectroscopy (2DCS) to characterize the folding mechanism of the mini-protein Beta3s. In this study Beta3s was folded by molecular dynamics (MD) simulation and intermediate conformational ensembles were identified. The one and two-dimensional correlation spectrum was calculated for the intermediate and native states of the mini-protein. A direct structure-spectra relationship was determined by analysis of conformational properties and specific residue contributions. We identified the structural origin of diagonal and off-diagonal peaks in the 2DCS spectra for the native and intermediate conformational ensembles in the folding mechanism. This work supports the implementation of computational techniques in conjunction with experimental 2DCS to study the folding mechanism of proteins. In addition to exploring the folding mechanism the work presented here can be applied in combination with experiment to refine and validate current molecular dynamics force fields.PACS Codes: 87.15.Cc, 87.15.hm, 87.15.hp

Highlights

The biological activities of proteins are determined by the specific three-dimensional structure and dynamical properties of the molecule
The major peak in the Ns conformation originated at 1653 cm-1 and was surrounded by a shoulder at 1630 cm-1 and another at 1671 cm-1 at Γ of 10 cm-1. (Figure 3, Table 2) The right shoulders correspond to the high v|| frequency b-sheet absorption while the central peak and left peaks result from increased random coil character and the v|| mode of the b-sheet in this conformation [16]
We have shown that 2DIR correlation spectroscopy (2DCS) IR spectra of proteins coupled with conformational sampling though folding calculations can reveal significant structural information about the ensemble evolution in the folding mechanism

Summary

Introduction

The biological activities of proteins are determined by the specific three-dimensional structure and dynamical properties of the molecule. The activity of misfolded proteins has been implicated in diseases including Alzheimer’s, Diabetes, Parkinson’s disease, many cancers and cancer-related syndromes, an understanding of the protein folding mechanism is of importance to pharmaceutical design and molecular biology [1,2,3,4,5]. Our understanding of protein folding has largely remained elusive due to the vast potential complexity of cooperative interactions involved in tracking such mechanisms [6,7,8]. A greater understanding of this process can be facilitated by further insight into both the structural and dynamical changes that occur during the folding process. A combination of experiment and calculations has recently been developed to monitor these changes in tandem

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Conclusion