Abstract
A tertiary structure governs, to a great extent, the biological activity of a protein in the living cell and is consequently a central focus of numerous studies aiming to shed light on cellular processes central to human health. Here, we aim to elucidate the structure of the Rift Valley fever virus (RVFV) L protein using a combination of in silico techniques. Due to its large size and multiple domains, elucidation of the tertiary structure of the L protein has so far challenged both dry and wet laboratories. In this work, we leverage complementary perspectives and tools from the computational-molecular-biology and bioinformatics domains for constructing, refining, and evaluating several atomistic structural models of the L protein that are physically realistic. All computed models have very flexible termini of about 200 amino acids each, and a high proportion of helical regions. Properties such as potential energy, radius of gyration, hydrodynamics radius, flexibility coefficient, and solvent-accessible surface are reported. Structural characterization of the L protein enables our laboratories to better understand viral replication and transcription via further studies of L protein-mediated protein–protein interactions. While results presented a focus on the RVFV L protein, the following workflow is a more general modeling protocol for discovering the tertiary structure of multidomain proteins consisting of thousands of amino acids.
Highlights
The three-dimensional structure of a protein governs to a great extent its biological activity, as molecules employ their tertiary structures to complement and bind each other [1]
From the analysis described in the paragraphs, which incorporates information from similar viral L proteins, it is clear that RAPTORX predictions on domain boundaries are unlikely to be correct; no further efforts were invested in this direction
For the L1 domain, we considered the structure of the aa 1–222 fragment extracted from extensive Molecular Dynamics (MD)
Summary
The three-dimensional (tertiary) structure of a protein governs to a great extent its biological activity, as molecules employ their tertiary structures to complement and bind each other [1]. Molecules 2019, 24, 1768 that a tertiary structure is key to obtaining a molecular-level understanding of cellular processes central to human health, resolving tertiary protein structures is a compelling research thrust in both dry and wet laboratories [2]. A collaborative project between our laboratories aims to better understand the replication of the Rift. Valley fever virus (RVFV) and, in particular, the key role of the protein encoded by the L segment of the RVFV RNA. RVFV is an arbovirus in the Bunyavirales order, Phenuiviridae family, and Phlebovirus genus. RVFV was discovered in the Great Rift Valley of Kenya in 1931 [3]. Since that time, is has caused periodic outbreaks in human and livestock populations throughout Africa, and has even spread into the Arabian
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