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Molecular motors and machines are essential for all cellular processes that together enable life. Built from proteins, with a wide range of properties, functionalities and performance characteristics, biological motors perform complex tasks and can transduce chemical energy into mechanical work more efficiently than human-made combustion engines. Sophisticated studies of biological protein motors have led to much structural and biophysical information and the development of models for motor function. However, from the study of highly evolved, biological motors it remains difficult to discern detailed mechanisms, for example about the relative role of different force generation mechanisms, or how information is communicated across a protein to achieve the necessary coordination. A promising, complementary approach to answering these questions is to build synthetic protein motors from the bottom up. Indeed, much effort has been invested in functional protein design, but so far, the ‘holy grail’ of designing and building a functional synthetic protein motor has not been realized. The purpose of ArtMotor is to design and build functional, synthetic protein motors capable of moving and transducing energy, based on existing, non-motor protein modules of known molecular function. Harnessing the synergy of expertise in computational protein design, structural and molecular biology, and single-molecule detection, we will use a two-pronged approach to (a) construct relatively simple protein motors that will require external control, while (b) construct, step by step, an autonomous protein motor capable of moving along a track. Such a functional, synthetic protein will constitute a ground-breaking advance in synthetic biology, physics and engineering. In addition to gaining new insights into mechanisms of energy transduction in proteins, we will also inspire other, complex protein designs that may lead to advances in fields from enzyme design to nano-engineering.

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