极化蛋白专一性电荷在HIV-1蛋白酶-抑制剂结合自由能预测中的应用

doi:10.19596/j.cnki.1001-246x.7752

计算物理 ›› 2018, Vol. 35 ›› Issue (3): 330-334.DOI: 10.19596/j.cnki.1001-246x.7752

极化蛋白专一性电荷在HIV-1蛋白酶-抑制剂结合自由能预测中的应用

李宇辰, 冯国强, 段莉莉

山东师范大学, 济南 250000

收稿日期:2017-08-31 修回日期:2017-09-06 出版日期:2018-05-25 发布日期:2018-05-25
通讯作者: 段莉莉,E-mail:pig5678@163.com
作者简介:李宇辰(1993-),男,硕士研究生,研究方向为生物物理、生物分子的量子力学计算、计算机辅助药物设计等,E-mail:519278134@qq.com
基金资助:
国家自然科学基金（11574184）及山东省优青项目（ZR2016JL003）资助

Application of Protein-specific Polarized Charge on HIV-1 Protease-Inhibitor Binding Free Enengy

LI Yuchen, FENG Guoqiang, DUAN Lili

Shandong Normal University, Jinan 250000, China

Received:2017-08-31 Revised:2017-09-06 Online:2018-05-25 Published:2018-05-25

摘要/Abstract

摘要： 对人类免疫缺陷病毒（HIV-1）蛋白酶-抑制剂复合物分别在AMBER力场及极化专一性蛋白电荷（PPC）下进行10 ns的分子动力学模拟（MD），并用MM/PBSA方法计算结合自由能.PPC是基于线性标度的量子力学计算的静电势拟合的蛋白质电荷，能够更准确地描述蛋白质所处的静电环境.结果表明：PPC电荷计算的结合自由能比AMBER力场计算的结合自由能更接近实验值.

关键词: HIV-1蛋白酶, 极化蛋白专一性电荷, 结合自由能

Abstract: Molecular dynamics simulations up to 10 ns are carried out to study binding of inhibitor to HIV-1 protease using standard AMBER force field and polarized protein-specific charge (PPC). Binding free energy was calculated by MM/PBSA method.PPC is derived from quantum mechanical calculation for protein in solution and therefore it includes electronic polarization effect. It shows that binding free energy calculated with PPC charge is closer to experimental result than that with AMBER force field.

Key words: HIV-1 protease, polarized protein-specific charge, binding free energy

中图分类号:

李宇辰, 冯国强, 段莉莉. 极化蛋白专一性电荷在HIV-1蛋白酶-抑制剂结合自由能预测中的应用[J]. 计算物理, 2018, 35(3): 330-334.

LI Yuchen, FENG Guoqiang, DUAN Lili. Application of Protein-specific Polarized Charge on HIV-1 Protease-Inhibitor Binding Free Enengy[J]. CHINESE JOURNAL OF COMPUTATIONAL PHYSICS, 2018, 35(3): 330-334.

参考文献

[1] NAVIA M A, FITZGERALD P M, MCKEEVER B M, et al. Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1[J]. Nature 1998, 337(6208):615-620.
[2] WLODAWER A, VONDRASEK J. Inhibitors of HIV-1 protease:A major success of structure-assisted drug design[J]. Annu Rev Biophys Biomol Struct, 1998, 27:249-284.
[3] LU Yipin, YANG Chaoyie, WANG Shaomeng. Binding free energy contributions of interfacial waters in HIV-1 protease/inhibitor complexes[J]. J Am Chem Soc, 2006, 128(36):11830-11839.
[4] DUAN L L, TONG Yan, MEI Ye, et al. Quantum study of HIV-1 protease-bridge water interaction[J]. J Chem Phys, 1998, 127(14):145101.
[5] PENG Bo, LI Hanlin, LU Benzhuo. Electrostatic calculation in biomolecular modeling[J]. Chinese Journal of Computational Physics, 2015, 32(2):127-159.
[6] DUAN L L, MEI Ye, LI Yongle, et al. Simulation of the thermodynamics of folding and unfolding of the trp-cage mini-protein TC5b using different combinations of force fields and solvation models[J]. Sci China Ser, 2010, B 53:196-201.
[7] WANG L Z, DUAN L L. Isothermal crystallization of a single polyethylene chain induced by graphene:A molecular dynamics simulation[J]. Comput Theor Chem, 2012,1002:59-63.
[8] DUAN L L, ZHU Tong, MEI Ye, et al. An implementation of hydrophobic force in implicit solvent molecular dynamics simulation for packed proteins[J]. J Mol Model, 2013, 19:2605-2612.
[9] LI Z C, DUAN L L, FENG G Q, et al. All-atom direct folding simulation for proteins using the accelerated molecular dynamics in implicit solvent model[J]. Chinese Phys Lett, 2015, 32(11):118701.
[10] JI C G, MEI Y, ZHANG J Z H. Developing polarized protein-specific charges for protein dynamics:MD free energy calculation of pKa shifts for Asp26/Asp20 in thioredoxin[J]. Biophys J, 2008, 95(3):1080-1088.
[11] DUAN L L, GAO Ya, MEI Ye, et al. Folding of helix is critically stabilized by polarization of backbone hydrogen bonds:Study in explicit water[J]. J Phys Chem B, 2012,116:3430-3435.
[12] JI C G, ZHANG J Z H. Protein polarization is critical to stabilizing AF-2 and helix-2' domains in ligand binding to PPAR-γ[J]. J Am Chem Soc, 2008, 50:17129-17133.
[13] DUAN L L, MEI Y, ZHANG Q G, et al. Intra-protein hydrogen bonding is dynamically stabilized by electronic polarization[J]. J Chem Phys, 2009, 130(11):115102.
[14] JORGENSEN W L, THOMAS L L. Perspective on free-energy perturbation calculations for chemical equilibria[J]. J Chem Theory Comput, 2008, 4:869-876.
[15] YUAN Bin. Level set parallel highly accurate evolution based on GPU cluster[J]. Chinese Journal of Computational Physics, 2016, 33(3):253-265.
[16] ZACHARIAS M, STRAATSMA T P, MCCAMMON J A. Separation-shifted scaling, a new scaling method for Lennard-Jones interactionsin thermodynamic integration[J]. J Chem Phys, 1994, 100:9025-9031.
[17] CORNELL W D, CIEPLAK P, BAYLY C I, et al. Application of RESP charges to calculate conformational energies, hydrogenbond energies, and free energies of solvation[J]. J Am Chem Soc, 1993, 115:9620-9631.
[18] ZHANG D W, ZHANG J Z H. Molecular fractionation with conjugate caps for full quantum mechanical calculation of protein molecule interaction energy[J]. J Chem Phys, 2003, 119(7):3599-3605.
[19] SUN H Y, LI Y Y, TIAN S, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDBbind data set[J]. Phys Chem Chem Phys, 2014, 16:16719-16729.
[20] SUN H Y, LI Y Y, TIAN S, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 5. Improved docking performance by using high solute dielectric constant MM/GBSA and MM/PBSA rescoring[J]. Phys Chem Chem Phys, 2014, 16:22035-22045.
[21] XU L, SUN H Y, LI Youyong, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 3. The impact of force fields and ligand charge models[J]. J Phys Chem, B 2013, 117:8408-8421.
[22] MA Zhibo. Physics evoked cloud method:A versatile systematic method for numerical simulations[J]. Chinese Journal of Computational Physics, 2017, 34(3):261-272.
[23] CHEN J Z, WANG J N, ZHU W L, et al. A computational analysis of binding modes and conformation changes of MDM2 induced by p53 and inhibitor bindings[J]. J Comput Aided Mol Des, 2013, 27:965-974.
[24] DUAN L L, LIU X, ZHANG J Z H. Interaction entropy:A new paradigm for highly efficient and reliable computation of protein-ligand binding free energy[J]. J Am Chem Soc, 2016, 138:5722-5728.
[25] SANNER M F, OLSON A J, SPEHNER J C. Reduced surface:An efficient way to compute molecular surfaces[J]. Biopolymers, 1996, 38(3):305-320.
[26] NGUYEN D T, CASE D A. On finding stationary states on large-molecule potential energy surfaces[J]. J Phys Chem, 1985, 89(19):4020-4026.

极化蛋白专一性电荷在HIV-1蛋白酶-抑制剂结合自由能预测中的应用

Application of Protein-specific Polarized Charge on HIV-1 Protease-Inhibitor Binding Free Enengy

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

作者中心

审稿中心

期刊浏览

期刊介绍

[1]	王兴炜, 宋晓书. 理论研究OH⁺离子电子态光谱及跃迁性质[J]. 计算物理, 2021, 38(6): 729-734.
[2]	周卓彦, 刘玉柱, 陈宇, 张昕阳, 孙卓怡. 丙烯醛在外电场中的解离性质[J]. 计算物理, 2021, 38(6): 722-728.
[3]	丁永龙, 胡琳萍, 张瑞勤. 一种基于迭代子空间直接求逆算法的高效子空间混合算法[J]. 计算物理, 2021, 38(4): 418-422.
[4]	吴言, 刘思琪, 李胜强. 芯片表面的冷极性分子静电阱与微阱阵列[J]. 计算物理, 2019, 36(4): 483-490.
[5]	韩晓琴, 肖夏杰. PO_X(X=1,2)的光谱常数与从头算势能曲线[J]. 计算物理, 2019, 36(1): 106-112.
[6]	韩玉龙, 孙辉, 孙金芳, 程军, 凤尔银. Be-CO(X¹∑⁺)体系的冷碰撞动力学[J]. 计算物理, 2018, 35(5): 626-630.
[7]	伍冬兰, 谭彬, 温玉锋, 曾学锋, 谢安东. 基于多参考组态方法研究MgI分子激发态的光谱[J]. 计算物理, 2018, 35(4): 469-474.
[8]	何君博, 刘玉柱, 林华, 葛英健, 韩顺. 外电场作用下黄曲霉素B₁的分子结构和光谱[J]. 计算物理, 2018, 35(3): 335-342.
[9]	王彬彬, 韩永昌. HeH⁺体系光缔合反应的动力学研究[J]. 计算物理, 2018, 35(3): 343-349.
[10]	孟续军, 王瑞利. 含温有界原子理论体系下电子状态方程不确定度的量化计算[J]. 计算物理, 2018, 35(2): 138-150.
[11]	林艳, 刘芸, 彭清维, 魏晓楠, 唐延林. 基于密度泛函理论的5~10元瓜环结构参数与前线轨道的计算[J]. 计算物理, 2018, 35(2): 221-229.
[12]	张翔云, 刘玉柱, 尹文怡, 马馨宇, 秦朝朝. 外电场作用下BrCl分子的物理特性与光谱[J]. 计算物理, 2018, 35(2): 230-234.
[13]	柳福提, 张淑华, 程晓洪. 耦合形貌对Si₄团簇电子输运影响的第一性原理计算[J]. 计算物理, 2018, 35(2): 235-241.
[14]	李胜强. 一种针对弱场搜寻态冷极性分子的可控静电表面囚禁方案[J]. 计算物理, 2017, 34(6): 731-739.
[15]	韩玉龙, 孙辉, 孙金芳, 张云玲, 凤尔银. Be-CO体系的相互作用势和光谱预测[J]. 计算物理, 2017, 34(5): 619-625.