Many proteins select from a small repertoire of 3-dimensional folds retained over evolutional timescales and recruited for different functions, with changes in local structure and sequence to enable specificity. Recent studies have revealed the evolutionary constraints on protein dynamics to achieve function. The significance of protein dynamics in simultaneously satisfying conformational flexibility/malleability and stability/precision requirements becomes clear upon dissecting the spectrum of equilibrium motions accessible to fold families. Accessibility to highly conserved global modes of motions shared by family members, to low-to-intermediate-frequency modes that distinguish subfamilies and confer specificity, and to conserved high-frequency modes ensuring chemical precision and core stability underlies functional specialization while exploiting highly versatile folds. These design principles are illustrated for the family of PDZ domains.

许多蛋白质从在进化时间尺度上保留并被招募用于不同功能的 3 维折叠的小库中进行选择，并通过改变局部结构和序列来实现特异性。最近的研究揭示了蛋白质动力学实现功能的进化限制。通过剖析折叠家族可获得的平衡运动谱，蛋白质动力学在同时满足构象灵活性/延展性和稳定性/精度要求方面的重要性变得清晰。可访问由家庭成员共享的高度保守的全局运动模式，以及区分亚家族并赋予特异性的中低频率模式，并且保守的高频模式确保化学精度和核心稳定性是功能专业化的基础，同时利用高度通用的折叠。这些设计原则针对 PDZ 域系列进行了说明。