Bille Anna, Mohanty Sandipan, Irbäck Anders
Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
Jülich Supercomputing Centre, Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich, Germany.
J Chem Phys. 2016 May 7;144(17):175105. doi: 10.1063/1.4948462.
Using Monte Carlo methods, we explore and compare the effects of two protein crowders, BPTI and GB1, on the folding thermodynamics of two peptides, the compact helical trp-cage and the β-hairpin-forming GB1m3. The thermally highly stable crowder proteins are modeled using a fixed backbone and rotatable side-chains, whereas the peptides are free to fold and unfold. In the simulations, the crowder proteins tend to distort the trp-cage fold, while having a stabilizing effect on GB1m3. The extent of the effects on a given peptide depends on the crowder type. Due to a sticky patch on its surface, BPTI causes larger changes than GB1 in the melting properties of the peptides. The observed effects on the peptides stem largely from attractive and specific interactions with the crowder surfaces, and differ from those seen in reference simulations with purely steric crowder particles.
我们使用蒙特卡罗方法，探索并比较了两种蛋白质拥挤剂，即抑肽酶（BPTI）和GB1，对两种肽（紧密螺旋的色氨酸笼肽和形成β-发夹结构的GB1m3）折叠热力学的影响。热稳定性高的拥挤剂蛋白采用固定主链和可旋转侧链进行建模，而肽则可自由折叠和展开。在模拟中，拥挤剂蛋白倾向于扭曲色氨酸笼肽的折叠结构，同时对GB1m3具有稳定作用。对给定肽的影响程度取决于拥挤剂的类型。由于其表面存在粘性区域，抑肽酶（BPTI）比GB1在肽的熔解特性方面引起的变化更大。观察到的对肽的影响主要源于与拥挤剂表面的吸引力和特异性相互作用，并且与纯空间拥挤剂颗粒的参考模拟中观察到的影响不同。
