Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J Biomol Struct Dyn. 2023;41(21):11510-11517. doi: 10.1080/07391102.2023.2173298. Epub 2023 Jan 30.
The octanol-water partition coefficient of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) was investigated using atomistic molecular dynamics simulations via thermodynamic integration and multistate Bennett acceptance ratio methods. The GAFF and CHARMM36 force fields were used with six water models widely used in molecular dynamics simulations. The OPC4 water model provided the best agreement with the experimental octanol-water partition coefficient of DPPC using the two force fields. However, there is still plenty of room for improvement in water models with correct estimation of surface tension that uses better and suitable non-bonded interaction parameters between water-water and water-DPPC. The Gibbs free energy of transferring DPPC from octanol to water phase was calculated to be 19.8 ± 0.3 and 20.2 ± 0.3 kcal mol, giving a partition coefficient of 14.5 ± 0.4 and 14.8 ± 0.3 for the GAFF and CHARMM36 force fields, respectively. This study reinforces the importance of developing new water models that reproduce experimental surface tensions to reconcile the water-water and water-DPPC non-bonded interactions and the existing discrepancy between experimental measurements of amphiphilic molecules that are important in many areas of scientific applications and industry such as biophysics, surfactant, colloids, membranes, medicine, nanotechnology, and food and pharmaceutical industries, and so on. It raises two important open questions: Is the experimental octanol-water partition coefficient of DPPC reliable? Or is its calculation accurate using the OPC4 water model? With respect to the experimental measurements, there may be non-treated aspects such as the formation of aggregates in aqueous phase and limit of detection of the applied method. And, in the calculation, some effects are not possible to be considered in a correct way or viable time such as calculating quantum effects, sampling all conformations, considering phase transitions, and correctly evaluating the intermolecular forces to estimate an accurate surface tension.Communicated by Ramaswamy H. Sarma.
使用热力学积分和多态 Bennett 接受率方法，通过原子分子动力学模拟研究了 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱 (DPPC) 的辛醇-水分配系数。使用广泛用于分子动力学模拟的六种水模型，分别使用 GAFF 和 CHARMM36 力场进行了研究。OPC4 水模型在两种力场下与 DPPC 的实验辛醇-水分配系数具有最佳的一致性。然而，仍有很大的改进空间，需要使用更好和合适的非键相互作用参数来正确估计表面张力，以改进水模型，使水-水和水-DPPC 之间的非键相互作用更准确。计算 DPPC 从辛醇相转移到水相的吉布斯自由能为 19.8±0.3 和 20.2±0.3 kcal/mol，GAFF 和 CHARMM36 力场的分配系数分别为 14.5±0.4 和 14.8±0.3。这项研究强调了开发新的水模型的重要性，这些模型可以重现实验表面张力，以协调水-水和水-DPPC 的非键相互作用，以及在生物物理、表面活性剂、胶体、膜、医学、纳米技术和食品与制药工业等许多科学应用和工业领域中重要的两亲分子的实验测量之间存在的差异。它提出了两个重要的开放性问题：DPPC 的实验辛醇-水分配系数是否可靠？或者使用 OPC4 水模型计算是否准确？关于实验测量，可能存在未处理的方面，例如水相中的聚集形成和应用方法的检测限。在计算中，一些效应不可能以正确或可行的方式考虑，例如计算量子效应、采样所有构象、考虑相变以及正确评估分子间力以准确估计表面张力。由 Ramaswamy H. Sarma 传达。
