MD-TSPC4: Computational Method for Predicting the Thermal Stability of I-Motif.

Amen Shamim,Maria Razzaq,Kyeong Kyu Kim

doi:10.3390/ijms22010061

Abstract

I-Motif is a tetrameric cytosine-rich DNA structure with hemi-protonated cytosine: cytosine base pairs. Recent evidence showed that i-motif structures in human cells play regulatory roles in the genome. Therefore, characterization of novel i-motifs and investigation of their functional implication are urgently needed for comprehensive understanding of their roles in gene regulation. However, considering the complications of experimental investigation of i-motifs and the large number of putative i-motifs in the genome, development of an in silico tool for the characterization of i-motifs in the high throughput scale is necessary. We developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic simulation. By assuming that the flexibility of loops in i-motifs correlated with thermal stability within certain temperature ranges, we evaluated the correlation between the root mean square deviations (RMSDs) of model structures and the thermal stability as the experimentally obtained melting temperature (Tm). Based on this correlation, we propose an equation for Tm prediction from RMSD. We expect this method can be useful for estimating the overall structure and stability of putative i-motifs in the genome, which can be a starting point of further structural and functional studies of i-motifs.

Highlights

Received: 24 November 2020 Accepted: 17 December 2020 Published: 23 December 2020Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Genomic DNA can adopt various conformations including the canonical right-handed B-form and non-B form DNA or the noncanonical DNA including guaninequadruplexes (G4), cytosine-quadruplexes (C4), triplexes, Z-DNA, cruciform and hairpins [1,2,3,4,5,6]
To provide one possible solution to this issue, we developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic (MD) simulation
We developed a new computational method, MD-TSPC4, that is used for estimating the thermal or structural stability in terms of providing the Tm value (Figure 6)

Summary

Introduction

Received: 24 November 2020 Accepted: 17 December 2020 Published: 23 December 2020Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Genomic DNA can adopt various conformations including the canonical right-handed B-form and non-B form DNA or the noncanonical DNA (ncDNA) including guaninequadruplexes (G4), cytosine-quadruplexes (C4), triplexes, Z-DNA, cruciform and hairpins [1,2,3,4,5,6]. The ncDNAs are formed in repeated sequences in the genome and participate in various biological functions such as controlling replication, maintaining genome integrity and regulating transcription and translation activities [7,8]. The genome-wide identification and characterization of G4s in various organisms have been reported in experimental and computational approaches [18,19,20,21,22]. These findings have shown that G4s are present in various locations in the genome but are enriched in gene promoters in human and mouse genomes compared with other non-mammal species [23]

Methods

Results

Conclusion