After translation, nascent proteins must escape the ribosomal exit tunnel to attain complete folding to their native states. This escape process also frees up the ribosome tunnel for a new translation job. In this study, we investigate the impacts of energetic interactions between the ribosomal exit tunnel and nascent proteins on the protein escape process by molecular dynamics simulations using partially coarse-grained models that incorporate hydrophobic and electrostatic interactions of the ribosome tunnel of Haloarcula marismortui with nascent proteins. We find that, in general, attractive interactions slow down the protein escape process, whereas repulsive interactions speed it up. For the small globular proteins considered, the median escape time correlates with both the number of hydrophobic residues, N_h, and the net charge, Q, of a nascent protein. A correlation coefficient exceeding 0.96 is found for the relation between the median escape time and a combined quantity of N_h + 5.9Q, suggesting that it is ∼6 times more efficient to modulate the escape time by changing the total charge than the number of hydrophobic residues. The estimated median escape times are found in the submillisecond-to-millisecond range, indicating that the escape does not delay the ribosome recycling. For various types of the tunnel model, with and without hydrophobic and electrostatic interactions, the escape time distribution always follows a simple diffusion model that describes the escape process as a downhill drift of a Brownian particle, suggesting that nascent proteins escape along barrier-less pathways at the ribosome tunnel.

翻译后，新生蛋白质必须逃离核糖体出口通道才能完全折叠到它们的天然状态。这种逃逸过程还为新的翻译工作释放了核糖体隧道。在这项研究中，我们通过分子动力学模拟研究了核糖体出口隧道和新生蛋白质之间的能量相互作用对蛋白质逃逸过程的影响，该模拟使用部分粗粒度模型，该模型结合了Haloarcula marismortui核糖体隧道与新生蛋白质的疏水和静电相互作用. 我们发现，一般来说，有吸引力的相互作用会减慢蛋白质逃逸过程，而排斥性的相互作用会加速它。对于所考虑的小球状蛋白质，中值逃逸时间与疏水残基的数量相关，N _h和新生蛋白质的净电荷Q。中值逃逸时间与N _h  + 5.9 Q的组合量之间的相关系数超过 0.96，表明通过改变总电荷来调节逃逸时间的效率比疏水残基的数量高 6 倍。估计的中值逃逸时间在亚毫秒到毫秒范围内，表明逃逸不会延迟核糖体循环。对于各种类型的隧道模型，无论有无疏水和静电相互作用，逃逸时间分布始终遵循一个简单的扩散模型，该模型将逃逸过程描述为布朗粒子的下坡漂移，表明新生蛋白质沿着无屏障途径逃逸在核糖体隧道。