Plotinus

An Ontology for Facilitating Discussion of Catalytic Strategies of RNA-Cleaving Enzymes

“…Although concerted and stepwise mechanisms are both possible, an idealized transition state (or metastable intermediate) is a dianionic pentavalent phosphorane in a trigonal bipyramidal geometry with nucleophile O2′ and leaving group O5′ ligands occupying apical positions (O2′-P-O5′ angle near 17 to 180°) and the formal (2−) charge delocalized between the O2′, O5′ and non-bridge phosphoryl oxygens (NPOs) ( Figure 1,right). Naturally occurring protein and RNA enzymes, as well as engineered enzymes such as DNAzymes, use multiple catalytic strategies in concert to enhance the rate of RNA cleavage by factors of typically 10 5 to 10 11 -fold [1][2][3][4]16 . Breaker has suggested a simplified framework for discussion of four basic catalytic strategies for RNA cleavage 16 , designated α, β, γ, and δ, as illustrated in Figure 1.…”

“…Naturally occurring protein and RNA enzymes, as well as engineered enzymes such as DNAzymes, use multiple catalytic strategies in concert to enhance the rate of RNA cleavage by factors of typically 10 5 to 10 11 -fold [1][2][3][4]16 . Breaker has suggested a simplified framework for discussion of four basic catalytic strategies for RNA cleavage 16 , designated α, β, γ, and δ, as illustrated in Figure 1. Concepts and terminology discussed in this Perspective apply to all enzymes catalyzing RNA cleavage via 2'-O-transphosphorylation, however we have focused our discussion and examples on small nucleolytic ribozymes.…”

“…Nucleolytic ribozymes serve as platforms for the design of new biomedical technology 13 and therapeutics [10][11] , and as models for our understanding of RNA catalysis and its implications for theories of evolution 18 . The central challenge is to gain a predictive understanding of precisely how these small RNA molecules, with their limited repertoire of chemical functional groups, are able to function as "high-speed" ribozymes 16 . Such an understanding would enable molecular engineering and guide the design of new catalytic RNA-based technology 13 and medicine [10][11] .…”

“…21 The first factor identified by Breaker was that "researchers frequently use different terms to discuss the same catalytic effects", and suggested that the community adopt the framework illustrated in Figure 1 for discussion of catalytic strategies for RNA cleavage. 16 This framework has been useful in facilitating discussion of RNA cleavage reactions 16 for over 15 years, but as more detailed mechanistic data emerge, there is need to accommodate increased specificity and resolution of our description of catalysis. Toward that end, we propose to develop an ontology for discussion of catalytic strategies of RNA cleaving enzymes that stratifies Breaker's original framework 16 into different levels of contribution for each strategy in order to enable more precise interpretation of mechanism in the context of structure and bonding.…”

Cartesian Dualism and Plotinus’ Philosophy of Mind

“…In what follows I will address some interpretations of Plotinus' philosophy I find problematic. I will first address the notion of Plotinus as the first Cartesian, mostly advocated by Dillon (1990) and Emilsson (2017). In addressing the notion, I will try to show that this kind of comparison is misleading and hermeneutically unjustified.…”