Inability to Perform Chemistry with Direct Positional Control
Our current methods do not allow precise control over the positional placement of atoms or groups during chemical synthesis, limiting our ability to build molecules with atomic precision. A general-purpose approach to atomically precise fabrication was envisioned by Drexler in the 1980s and Feynman in the late 1950s. DNA origami made a leap in 2006, but DNA is in some key ways a much less precise and versatile nanoscale building material than proteins/peptides. A promising path would extend “DNA origami” to “protein carpentry” by adapting Beta Solenoid proteins, or other modular protein components with programmable binding properties, as lego-like building blocks and then using the latter to construct massively parallel protein-based 3D printers for lego-like covalent assembly of a restricted set of chemical building blocks. This one is riskier: how programmably can we really control protein assembly, and could we bootstrap from initial crappy prototype protein-carpentry-and-or-DNA-origami-based molecular 3D printers to genuinely useful ones?
Foundational Capabilities (6)
Explore methods for molecular-scale 3D printing, which would enable the precise assembly of molecules layer by layer.
This would in principle move us towards a general-purpose approach to atomically precise fabrication as envisioned by Drexler in the 1980s and Feynman in the late 1950s. DNA origami made a leap in 2006, but DNA is in some key ways a much less precise and versatile nanoscale building material than proteins/peptides. A promising path would extend “DNA origami” to “protein carpentry” by adapting Beta Solenoid proteins, or other modular protein components with programmable binding properties, as lego-like building blocks and then using the latter to construct massively parallel protein-based 3D printers for lego-like covalent assembly of a restricted set of chemical building blocks. This one is riskier: how programmably can we really control protein assembly, and could we bootstrap from initial crappy prototype protein-carpentry-and-or-DNA-origami-based molecular 3D printers to genuinely useful ones?
Safety consideration: https://iopscience.iop.org/article/10.1088/0957-4484/15/8/001
Strategy consideration: https://www.effectivealtruism.org/articles/ea-global-2018-paretotopian-goal-alignment
Utilize cell-free platforms that enable synthetic biology outside of living cells, thereby bypassing the limitations of evolved cellular machinery.
Design polymers that are not limited to amino acids and are directly specified in three dimensions, enabling precise positional control in synthesis and potentially broader or more robust functions than proteins.
Investigate the feasibility of vacuum mechanosynthesis—a process that uses mechanical forces under vacuum conditions to construct molecules with high positional precision.
Create enzymes specifically engineered via quantum chemical methods and de novo protein design, which can precisely catalyze reactions at defined positions.
Current fabrication methods allow us to work at macroscopic scales (10^0 m) down to the nanometer scale (10^-8 m) with photolithography, and further down to the atomic scale (10^-10 m) with proteins. However, directly bridging from macroscopic to atomic scales (10^0 m to 10^-10 m) for nanotechnology applications remains a significant challenge. A key obstacle is the lack of effective interfaces between single addressable electrodes and proteins.