Department of Physics and Astronomy, University of Southern Mississippi, Hattiesburg, Mississippi, United States of America.
PLoS One. 2013 Oct 18;8(10):e76069. doi: 10.1371/journal.pone.0076069. eCollection 2013.
Interaction with the solvent plays a critical role in modulating the structure and dynamics of a protein. Because of the heterogeneity of the interaction strength, it is difficult to identify multi-scale structural response. Using a coarse-grained Monte Carlo approach, we study the structure and dynamics of a protein (H3.1) in effective solvent media. The structural response is examined as a function of the solvent-residue interaction strength (based on hydropathy index) in a range of temperatures (spanning low to high) involving a knowledge-based (Miyazawa-Jernigan(MJ)) residue-residue interaction. The protein relaxes rapidly from an initial random configuration into a quasi-static structure at low temperatures while it continues to diffuse at high temperatures with fluctuating conformation. The radius of gyration (Rg ) of the protein responds non-monotonically to solvent interaction, i.e., on increasing the residue-solvent interaction strength (fs ), the increase in Rg (fs ≤fsc ) is followed by decay (fs ≥fsc ) with a maximum at a characteristic value (fsc ) of the interaction. Raising the temperature leads to wider spread of the distribution of the radius of gyration with higher magnitude of fsc . The effect of solvent on the multi-scale (λ: residue to Rg ) structures of the protein is examined by analyzing the structure factor (S( q ),|q| = 2π/λ is the wave vector of wavelength, λ) in detail. Random-coil to globular transition with temperature of unsolvated protein (H3.1) is dramatically altered by the solvent at low temperature while a systematic change in structure and scale is observed on increasing the temperature. The interaction energy profile of the residues is not sufficient to predict its mobility in the solvent. Fine-grain representation of protein with two-node and three-node residue enhances the structural resolution; results of the fine-grained simulations are consistent with the finding described above of the coarse-grained description with one-node residue.
溶剂相互作用在调节蛋白质的结构和动力学方面起着关键作用。由于相互作用强度的不均匀性，很难识别多尺度结构响应。我们使用粗粒度蒙特卡罗方法研究了蛋白质（H3.1）在有效溶剂介质中的结构和动力学。在一系列温度（从低到高）下，作为溶剂-残基相互作用强度（基于疏水性指数）的函数，研究了结构响应，其中涉及基于知识的（Miyazawa-Jernigan（MJ））残基-残基相互作用。在低温下，蛋白质从初始随机构象快速弛豫到准静态结构，而在高温下，蛋白质继续扩散，构象波动。蛋白质的回转半径（Rg）对溶剂相互作用呈非单调响应，即随着残基-溶剂相互作用强度（fs）的增加，Rg 的增加（fs≤fsc）后，随着特征值（fsc）的增加，Rg 衰减（fs≥fsc）。升高温度会导致回转半径分布的扩散范围更广，且 fsc 的幅度更高。通过详细分析结构因子（S（q），|q|=2π/λ，是波长的波矢，λ是长度标度），研究了溶剂对蛋白质多尺度（λ：残基到 Rg）结构的影响。未溶剂化蛋白质（H3.1）的随机卷曲到球形转变随着温度的升高而发生显著改变，而随着温度的升高，结构和尺度也发生了系统的变化。残基的相互作用能谱不足以预测其在溶剂中的迁移率。用两个节点和三个节点残基精细表示蛋白质提高了结构分辨率；用一个节点残基进行粗粒化描述的结果与上述精细粒化模拟的结果一致。
