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(1994 Drexler) Implementation strategies for molecular nanomachines: protein engineering and AFM-based molecular manipulation

“The goal of constructing artificial molecular machine systems able to perform mechanosynthesis is beyond the immediate reach of current laboratory techniques. Nonetheless, these systems can already be modeled in substantial detail, and existing techniques enable steps toward their implementation.

“Mechanosynthetic systems will rely on mechanical positioning to guide and control the molecular interactions of chemical synthesis. The effective concentration of a mechanically positioned species depends on the temperature and on the stiffness of the positioning system. These concentrations can be large (> 100 M) and localized on a molecular scale. Background concentrations can approach zero, thus enabling precise molecular control of the locations and sequences of synthetic operations. Researchers have developed concepts for mechanosynthetic systems and defined general technology requirements. One approach to the fabrication of molecular machine systems is the development of AFM-based mechanosynthetic devices. These would position molecules [note: not “atoms”] by binding them to (for example) antibody fragments attached to an AFM tip. Development of suitable monomers, binding sites, and reaction sequences would then be a basis for the fabrication of complex mechanical structures.

“Biological molecular machine systems rely on the self-assembly of folded polymers. A review of progress in protein engineering suggests that we have the means to design and synthesize protein-like molecules with well-defined structures and excellent stability. Success in this effort provides a basis for the design of self-assembling systems, and experience with the design and supramolecular assembly of smaller molecules is encouraging regarding the success of this next step.

“Development of a molecular machine technology promises a wide range of applications. Biological molecular machines synthesize proteins, read DNA, and sense a wide range of molecular phenomena. Artificial molecular machine systems could presumably be developed to perform analogous tasks, but with more stable structures and different results (e.g. reading DNA sequences into a conventional computer memory, rather than transcribing them into RNA). Self-assembling structures are widely regarded as a key to molecular electronic systems, which therefore share an enabling technology with molecular machine systems. Finally, studies suggest that the use of molecular machine systems to perform mechanosynthesis of diverse structures (including additional molecular machine systems) will enable the development and inexpensive production of a broad range of new instruments and products. Laboratory research directed toward this goal seems warranted.”

With link to abstract (above):

Drexler KE  (1994) “Molecular nanomachines: physical principles and implementation strategies” Annual  Review of  Biophysics and  Biomolecular  Structure 23:377-405