Drexler K E
Institute for Molecular Manufacturing, Palo Alto, California 94301.
Annu Rev Biophys Biomol Struct. 1994;23:377-405. doi: 10.1146/annurev.bb.23.060194.002113.
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 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.
构建能够进行机械合成的人工分子机器系统的目标，目前的实验室技术还无法立即实现。尽管如此，这些系统已经可以进行相当详细的建模，并且现有技术能够朝着实现它们的方向迈出步伐。机械合成系统将依靠机械定位来引导和控制化学合成的分子相互作用。机械定位物种的有效浓度取决于温度和定位系统的刚度。这些浓度可以很大（>100 M）并且在分子尺度上是局部化的。背景浓度可以接近零，从而实现对合成操作的位置和序列进行精确的分子控制。研究人员已经开发出了机械合成系统的概念，并确定了一般的技术要求。制造分子机器系统的一种方法是开发基于原子力显微镜（AFM）的机械合成装置。这些装置将通过将分子与（例如）附着在AFM针尖上的抗体片段结合来定位分子。然后，开发合适的单体、结合位点和反应序列将成为制造复杂机械结构的基础。生物分子机器系统依赖于折叠聚合物的自组装。对蛋白质工程进展的综述表明，我们有办法设计和合成具有明确结构和出色稳定性的类蛋白质分子。这项工作的成功为自组装系统的设计提供了基础，并且在小分子的设计和超分子组装方面的经验对于下一步的成功也很有鼓舞作用。分子机器技术的发展有望带来广泛的应用。生物分子机器合成蛋白质、读取DNA并感知多种分子现象。人工分子机器系统大概可以被开发来执行类似的任务，但具有更稳定的结构和不同的结果（例如将DNA序列读取到传统计算机内存中，而不是转录成RNA）。自组装结构被广泛认为是分子电子系统的关键所在，因此分子电子系统与分子机器系统共享一种使能技术。最后，研究表明，使用分子机器系统进行各种结构（包括其他分子机器系统）的机械合成，将能够开发并廉价生产出各种各样的新仪器和产品。针对这一目标的实验室研究似乎是有必要的。
