Using computational approaches to study dengue virus capsid assembly

Abstract

Dengue viral capsid plays a significant role in viral life cycle of dengue, especially in vial genome protection and virus-cell fusion. Revealing mechanisms of the viral capsid protein assembly may lead to the discovery of anti-viral drugs that inhibit the assembly of the viral capsid. The E and M-proteins are arranged into heterotetramers, which consists of two copies of E and M-protein. The heterotetramers are assembled into a highly ordered capsid. While many investigations of the interactions between E and M-proteins have been performed, there are very few studies on the interactions between the heterotetramers and their roles in capsid assembly. Utilizing a series of computational approaches, this study focuses on the assembly mechanism of the heterotetramers. Our electrostatic analyses lead to the identification of four binding modes between each two dengue heterotetramers that repeat periodically throughout the virus capsid. Among these four binding modes, heterotetramers in binding modes I, II and IV are attractive. But in the binding mode III the heterotetramers repel each other, making mode III a suitable target for drug design. Furthermore, MD simulations were performed following by salt bridges analysis. This study demonstrates that using computational approaches is a promising direction to study the dengue virus.

Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2

“…Besides the experimental studies, various computational studies have been conducted to investigate the interactions between SARS-CoV-2 S protein and ACE2. Some systematic comparison and analysis were performed on SARS-CoV-2 S protein RBD and ACE2 to identify potential intermediate hosts transmitting SARS-CoV-2 to humans (Salas et al, 2019 ). Some MD simulations revealed that the SARS-CoV-2 S protein-ACE2 binding is more temperature sensitive than SARS-CoV S protein-ACE2 binding (van der Schoot and Bruinsma, 2005 ).…”

StructureMan: A Structure Manipulation Tool to Study Large Scale Biomolecular Interactions

“…The charge distribution on capsomers mainly has two functions: First, the electrostatic interactions among capsomers play significant roles in assembling and stabilizing the whole capsid structure (Li et al, 2012a ; Salas et al, 2019 ; Xian et al, 2019 ). Second, electrostatic interactions between capsid and DNA/RNA stabilize the encapsidated genomic materials by neutralizing the repulsive forces between the DNA/RNAs (Bakker et al, 2012 ).…”

“…Previous studies on viral capsids have demonstrated the interactions between an individual capsomer and its adjacent capsomers are crucial in the capsid assembly process (Salas et al, 2019 ; Xian et al, 2019 ). Here we focused on the interaction between one capsomer and the rest of the capsid.…”

The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2

“…With the fast developments of computing technology, computational methods have been widely used in drug-related research [12], including protein-protein interactions [13,14], MD simulations [15], coarse-grained models [16], pH dependence of protein-protein interactions [17][18][19][20], etc. Our previous studies have applied multi-scale computational methods to study several pathogens [21][22][23][24][25] including the SARS-CoV-2 viruses [26,27], which revealed some mechanisms of the SARS-CoV-2 S protein. Additionally, many other research groups have made successful progress to understand the SARS-CoV-2 using computational methods [28,29].…”