Department of Materials Science and Engineering, Indian Institute of Technology Delhi, New Delhi 110016, India.
Center for Computational and Data Sciences, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
Phys Chem Chem Phys. 2023 Feb 15;25(7):5430-5442. doi: 10.1039/d2cp04238j.
A comprehensive understanding of crowding effects on biomolecular processes necessitates investigating the bulk thermodynamic and kinetic properties of the solutions with an accurate molecular representation of the crowded milieu. Recent studies have reparameterized the non-bonded dispersion interaction of solutes to precisely model intermolecular interactions, which would circumvent artificial aggregation as shown by the original force-fields. However, the performance of this reparameterization is yet to be assessed for concentrated crowded solutions in terms of investigating the hydration shell structure, energetics and dynamics. In this study, we perform molecular dynamics simulations of crowded aqueous solutions of five zwitterionic neutral amino acids (Gly, Ala, Thr, Pro, and Ser), mimicking the molecular crowding environment, using a modified AMBER ff99SB-ILDN force-field. We systematically examine and show that the reproducibility of the osmotic coefficients, density, viscosity and self-diffusivity of amino acids improves using the modified force-field in crowded concentrations. The modified force-field also improves the structuring of the solute solvation shells, solute interaction energy and convergence of tails of radial distribution functions, indicating reduction in the artificial aggregation. Our results also indicate that the hydrogen bonding network of water weakens and water molecules anomalously diffuse at small time scales in the crowded solutions. These results underscore the significance of examining the solution properties and anomalous hydration behaviour of water in crowded solutions, which have implications in shaping the structure and dynamics of biomolecules. The findings also illustrate the improvement in predicting bulk solution properties using the modified force-field, thereby providing an approach towards accurate modeling of crowded molecular solutions.
全面了解拥挤效应对生物分子过程的影响，需要用拥挤环境的准确分子描述来研究溶液的总体热力学和动力学性质。最近的研究已经重新参数化了溶质的非键分散相互作用，以精确模拟分子间相互作用，这将避免原始力场所示的人为聚集。然而，这种重新参数化的性能仍需在研究水合壳结构、能量和动力学方面，针对浓缩拥挤溶液进行评估。在这项研究中，我们使用修改后的 AMBER ff99SB-ILDN 力场，对五种两性中性氨基酸（甘氨酸、丙氨酸、苏氨酸、脯氨酸和丝氨酸）的拥挤水溶液进行分子动力学模拟，模拟分子拥挤环境。我们系统地检查并表明，在拥挤浓度下使用修改后的力场可以提高渗透压系数、密度、粘度和氨基酸的自扩散系数的重现性。修改后的力场还改善了溶质溶剂化壳的结构、溶质相互作用能和径向分布函数尾部的收敛性，表明人为聚集减少。我们的结果还表明，拥挤溶液中的水的氢键网络减弱，水分子在小时间尺度上异常扩散。这些结果强调了研究拥挤溶液中溶液性质和异常水合行为的重要性，这对塑造生物分子的结构和动力学具有重要意义。研究结果还说明了使用修改后的力场来预测总体溶液性质的改进，从而为拥挤分子溶液的精确建模提供了一种方法。
