AI 中文总结
该研究以β-内酰胺酶为模型，基于最小作用量原理验证分析蛋白质进化的新模型，考虑突变及相互作用对蛋白质稳定性和折叠动力学的影响，能快速准确识别最可能路径和最有效轨迹，解决了蛋白质进化相关未决问题并指明研究方向。
AI 中文摘要
蛋白质序列会因编码基因突变积累而随时间变化。准确识别祖先序列与衍生序列间最可能的进化路径和更高效轨迹仍是挑战，源于对驱动进化过程关键因素理解有限。本研究旨在通过验证新提出的基于最小作用量原理的机制模型来分析蛋白质进化，以β-内酰胺酶为经验特征进化模型。初步结果表明，考虑突变及其上下文依赖相互作用（上位性）对蛋白质稳定性及折叠动力学的影响后，最小作用量原理能让我们快速准确地同时识别最可能路径和最有效轨迹。研究还表明最可能的进化蛋白质路径是具有最有效轨迹的路径。总之，本研究解决了分子水平（恒定选择压力下）蛋白质进化主要因素的一些未决问题，并为定向进化和祖先序列重建等关键领域的未来研究指明方向。
英文摘要
Protein sequences change over time due to the accumulation of mutations in the genes that encode them. Nonetheless, accurately identifying the most probable evolutionary pathways and more efficient trajectories between an ancestral and a derived sequence remains a challenge. This difficulty stems from a limited understanding of the critical factors that drive the evolutionary process. This study aims to address this issue by validating a newly proposed mechanistic model (grounded on the principle of least action) for analyzing protein evolution, using beta-lactamase as an empirically characterized evolutionary model. The initial findings indicate that, after accounting for how mutations and the context-dependent interactions between them (epistasis) affect protein stability and, hence, the kinetics of protein folding, a resort to the principle of least action allows us to simultaneously identify the most probable pathways and the most efficient trajectories swiftly and accurately. These findings also suggest that the most probable evolutionary protein pathways are the ones that exhibit the most efficient trajectories. All in all, our study addresses several unanswered questions regarding the main factors that govern how protein evolves at the molecular level (under constant selection pressure) and outlines directions for future research in key fields such as directed evolution and ancestral sequence reconstruction.
Comments22 pages, 2 figures, 1 table
