Centre for Computational and Data Sciences, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
Phys Chem Chem Phys. 2020 Aug 24;22(32):18091-18101. doi: 10.1039/d0cp02402c.
Biomolecules evolve and function in the intracellular crowded environment that is densely packed with macromolecules. Yet, a microscopic understanding of the effects of such an environment on the conformational preferences of biomolecules remains elusive. While prior investigations have attributed crowding effects mainly to the excluded volume (size) effects of the crowders, very little is known about the effects exerted due to their chemical interactions. In this study, crowding effects of tri-alanine peptides on the collapse equilibria of generic hydrophobic polymer are investigated using molecular dynamics simulations. The role of weak, non-specific, attractive polymer-crowder interactions in modulating the polymer collapse equilibria is examined. The results highlight that crowding effects can lead to polymer compaction as well as unfolding depending on the strength of polymer-crowder interaction energy. Strongly interacting crowders weaken hydrophobic collapse (or unfold the polymer) at high volume fractions and induce polymer collapse only under dilute conditions. Weakly interacting crowders induce polymer collapse at all crowder concentrations. Interestingly, the thermodynamic driving forces for polymer collapse are remarkably different in the two cases. Strongly and weakly interacting crowders induce collapse by preferential adsorption and preferential depletion respectively. The findings provide new insights into the possible effects of interplay of intermolecular interactions in a crowded environment. The results have implications in understanding the impact of crowding in altering free energy landscapes of proteins.
生物分子在细胞内拥挤的环境中进化和发挥功能，该环境中充满了大分子。然而，对于这种环境对生物分子构象偏好的影响，我们仍然难以从微观上理解。虽然先前的研究主要归因于拥挤剂的排除体积（大小）效应，但对于由于其化学相互作用而产生的影响却知之甚少。在这项研究中，使用分子动力学模拟研究了三丙氨酸肽对通用疏水聚合物崩溃平衡的拥挤效应。研究了弱、非特异性、聚合物-拥挤剂吸引力在调节聚合物崩溃平衡中的作用。结果表明，拥挤效应可能导致聚合物紧缩以及展开，这取决于聚合物-拥挤剂相互作用能的强度。强相互作用的拥挤剂在高体积分数下削弱疏水崩溃（或使聚合物展开），并仅在稀溶液条件下诱导聚合物崩溃。弱相互作用的拥挤剂在所有拥挤剂浓度下都诱导聚合物崩溃。有趣的是，两种情况下聚合物崩溃的热力学驱动力有很大的不同。强相互作用和弱相互作用的拥挤剂分别通过优先吸附和优先耗尽来诱导聚合物崩溃。这些发现为在拥挤环境中分子间相互作用相互作用可能产生的影响提供了新的见解。研究结果对理解拥挤改变蛋白质自由能景观的影响具有重要意义。
