Analyzing the Geometry and Dynamics of Viral Structures: A Review of Computational Approaches Based on Alpha Shape Theory, Normal Mode Analysis, and Poisson–Boltzmann Theories

Abstract

The current SARS-CoV-2 pandemic highlights our fragility when we are exposed to emergent viruses either directly or through zoonotic diseases. Fortunately, our knowledge of the biology of those viruses is improving. In particular, we have more and more structural information on virions, i.e., the infective form of a virus that includes its genomic material and surrounding protective capsid, and on their gene products. It is important to have methods that enable the analyses of structural information on such large macromolecular systems. We review some of those methods in this paper. We focus on understanding the geometry of virions and viral structural proteins, their dynamics, and their energetics, with the ambition that this understanding can help design antiviral agents. We discuss those methods in light of the specificities of those structures, mainly that they are huge. We focus on three of our own methods based on the alpha shape theory for computing geometry, normal mode analyses to study dynamics, and modified Poisson–Boltzmann theories to study the organization of ions and co-solvent and solvent molecules around biomacromolecules. The corresponding software has computing times that are compatible with the use of regular desktop computers. We show examples of their applications on some outer shells and structural proteins of the West Nile Virus.

Polyelectrolytes: From Seminal Works to the Influence of the Charge Sequence

“…Recently, the structure of viruses where electrostatic interactions play an important role received increasing attention. The review [77] describes recent advances in understanding viral structures. Biophysics puts forward questions which are sometimes raised in the surfactant community regarding short-distance electrostatics, typically close to an interface [42,78] or dense charged media [55].…”

MinActionPath2: path generation between different conformations of large macromolecular assemblies by action minimization

“…To circumvent this problem, more terms are needed in the energy. The Go Model has been parametrized with this purpose in mind, including terms that are based on bond lengths, torsion angles, dihedral angles, and a van-der-Waals-like term ( 16 , 17 ). Note that the Go model only considers CA atoms and currently works only for proteins.…”

“…First, it allows to define the neighbours in the pairwise sums of the energy function using Delaunay triangulation ( 15 ), and second, it provides the option of using a Go-like model to define the potential in proteins ( 16 ). It has been shown that the use of such potential reduces the number of covalent bonds with unreasonable stereochemistry during the transition ( 17 ). The code has been entirely rewritten to enable the study of very large systems and the web interface now offers a user-friendly visualization of the resulting trajectory in the output.…”