Many biological functions are executed by molecular machines, which like man made motors consume energy and convert it into mechanical work. Biological machines have evolved to transport cargo, facilitate folding of proteins and RNA, remodel chromatin and replicate DNA. A common aspect of these machines is that their functions are driven by fuel provided by hydrolysis of ATP or GTP, thus driving them out of equilibrium. It is a challenge to provide a general framework for understanding the functions of biological machines, such as molecular motors (kinesin, dynein, and myosin), molecular chaperones, and helicases. Using these machines, whose structures have little resemblance to one another, as prototypical examples, we describe a few general theoretical methods that have provided insights into their functions. Although the theories rely on coarse-graining of these complex systems they have proven useful in not only accounting for many {} experiments but also address questions such as how the trade-off between precision, energetic costs and optimal performances are balanced. However, many complexities associated with biological machines will require one to go beyond current theoretical methods. We point out that simple point mutations in the enzyme could drastically alter functions, making the motors bi-directional or result in unexpected diseases or dramatically restrict the capacity of molecular chaperones to help proteins fold. These examples are reminders that while the search for principles of generality in biology is intellectually stimulating, one also ought to keep in mind that molecular details must be accounted for to develop a deeper understanding of processes driven by biological machines. Going beyond generic descriptions of {} behavior to making genuine understanding of {} functions will likely remain a major challenge for some time to come. In this context, the combination of careful experiments and the use of physics and physical chemistry principles will be useful in elucidating the rules governing the workings of biological machines.

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关于生物机器的理论观点

许多生物功能是由分子机器执行的，就像人造马达一样，它们会消耗能量并将其转换为机械功。生物机器已经发展为运输货物，促进蛋白质和RNA的折叠，重塑染色质和复制DNA。这些机器的一个共同方面是它们的功能由ATP或GTP水解提供的燃料驱动，从而使它们失去平衡。提供一个理解生物机器功能的通用框架是一项挑战，例如分子马达（驱动蛋白，动力蛋白和肌球蛋白），分子伴侣和解旋酶。使用这些结构互不相同的机器作为原型示例，我们描述了一些通用的理论方法，这些方法为它们的功能提供了见识。尽管理论依赖于这些复杂系统的粗粒度，但事实证明，这些理论不仅可用于进行许多{}实验，而且还可解决诸如如何平衡精度，能量成本和最佳性能之间的权衡等问题。然而，与生物机器相关的许多复杂性将要求人们超越当前的理论方法。我们指出，酶中的简单点突变可能会极大地改变功能，使运动双向发生或导致意想不到的疾病，或大大限制分子伴侣蛋白帮助蛋白质折叠的能力。这些例子提醒我们，尽管在生物学上寻求一般性原则是令人兴奋的，还应该记住，必须考虑分子的细节，以加深对生物机器驱动过程的了解。除了对{}行为的一般描述之外，对{}函数的真正理解可能仍将是未来一段时间的主要挑战。在这种情况下，精心的实验以及物理和物理化学原理的结合将有助于阐明控制生物机器工作的规则。