Posts Tagged ‘precisely’

The quantum properties of non-point particles

Quantum theory: it’s unreal We know that everything in the universe including particles have physical size. Even so for the past 50 years, the Standard Model of particle physics which many say has given us the most complete mathematical description of the particles and forces that shape our world ignores this fact and treats them […]

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Accurate de novo design of hyperstable constrained peptides

Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18–47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N–C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.

Emotionalisation, Neoliberalism and Academic Freedom in US

The boundaries of academic freedom in the US have shifted, argues Sam Binkley. What is at stake now is not only the freedom to think, speak and generate knowledge, but the freedom, even the requirement that one becomes a certain kind of person in order to think and speak in certain kinds of ways.

A Response to Dr. Swamidass’s Questions, Pt. 2: Answering the Questions

This is an ongoing discussion we are having with Dr. Swamidass over the question of Methodological Naturalism in science. For those who haven’t been keeping up, I posted Dr. Swamidass’s questions to critics of MN to UD a few weeks ago, then posted some of my questions for proponents of MN. Then, my first response […]

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