Periodic Table of Virus Capsids: Implications for Natural Selection and Design

Background: For survival, most natural viruses depend upon the existence of spherical capsids: protective shells of various sizes composed of protein subunits. So far, general evolutionary pressures shaping capsid design have remained elusive, even though an understanding of such properties may help in rationally impeding the virus life cycle and designing efficient nano-assemblies. Principal Findings: This report uncovers an unprecedented and species-independent evolutionary pressure on virus capsids, based on the the notion that the simplest capsid designs (or those capsids with the lowest ‘‘hexamer complexity’’, C h) are the fittest, which was shown to be true for all available virus capsids. The theories result in a physically meaningful periodic table of virus capsids that uncovers strong and overarching evolutionary pressures, while also offering geometric explanations to other capsid properties (rigidity, pleomorphy, auxiliary requirements, etc.) that were previously considered to be unrelatable properties of the individual virus. Significance: Apart from describing a universal rule for virus capsid evolution, our work (especially the periodic table) provides a language with which highly diverse virus capsids, unified only by geometry, may be described and related to each other. Finally, the available virus structure databases and other published data reiterate the predicted geometryderive

A Universal Trend among Proteomes Indicates an Oily Last Common Ancestor

Despite progresses in ancestral protein sequence reconstruction, much needs to be unraveled about the nature of the putative last common ancestral proteome that served as the prototype of all extant lifeforms. Here, we present data that indicate a steady decline (oil escape) in proteome hydrophobicity over species evolvedness (node number) evident in 272 diverse proteomes, which indicates a highly hydrophobic (oily) last common ancestor (LCA). This trend, obtained from simple considerations (free from sequence reconstruction methods), was corroborated by regression studies within homologous and orthologous protein clusters as well as phylogenetic estimates of the ancestral oil content. While indicating an inherent irreversibility in molecular evolution, oil escape also serves as a rare and universal reaction-coordinate for evolution (reinforcing Darwin's principle of Common Descent), and may prove important in matters such as (i) explaining the emergence of intrinsically disordered proteins, (ii) developing composition- and speciation-based “global” molecular clocks, and (iii) improving the statistical methods for ancestral sequence reconstruction.Chemistry and Chemical Biolog

Dynamic New World: Refining Our View of Protein Structure, Function and Evolution

Proteins are crucial to the functioning of all lifeforms. Traditional understanding posits that a single protein occupies a single structure (“fold”), which performs a single function. This view is radically challenged with the recognition that high structural dynamism—the capacity to be extra “floppy”—is more prevalent in functional proteins than previously assumed. As reviewed here, this dynamic take on proteins affects our understanding of protein “structure”, function, and evolution, and even gives us a glimpse into protein origination. Specifically, this review will discuss historical developments concerning protein structure, and important new relationships between dynamism and aspects of protein sequence, structure, binding modes, binding promiscuity, evolvability, and origination. Along the way, suggestions will be provided for how key parts of textbook definitions—that so far have excluded membership to intrinsically disordered proteins (IDPs)—could be modified to accommodate our more dynamic understanding of proteins

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h).

The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom-the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide's conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ =  - 100°  left-handed or right-handed?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone's internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d∕|d|, with range [-1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ) space. These maps fill in the 'dead space' within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis and trans backbones. The intuitiveness arises from the fact that d and θ provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h).

The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom-the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide's conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ =  - 100°  left-handed or right-handed?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone's internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d∕|d|, with range [-1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ) space. These maps fill in the 'dead space' within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis and trans backbones. The intuitiveness arises from the fact that d and θ provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity