蛋白质折叠模拟中的挑战：时间尺度、表示方法和分析
Challenges in protein folding simulations: Timescale, representation, and analysis.
作者信息
Freddolino Lydia, Harrison Christopher B, Liu Yanxin, Schulten Klaus
机构信息
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
出版信息
Nat Phys. 2010 Oct 1;6(10):751-758. doi: 10.1038/nphys1713.
Abstract
Experimental studies of protein folding processes are frequently hampered by the fact that only low resolution structural data can be obtained with sufficient temporal resolution. Molecular dynamics simulations offer a complementary approach, providing extremely high resolution spatial and temporal data on folding processes. The effectiveness of such simulations is currently hampered by continuing questions regarding the ability of molecular dynamics force fields to reproduce the true potential energy surfaces of proteins, and ongoing difficulties with obtaining sufficient sampling to meaningfully comment on folding mechanisms. We review recent progress in the simulation of three common model systems for protein folding, and discuss how recent advances in technology and theory are allowing protein folding simulations to address their current shortcomings.
摘要
蛋白质折叠过程的实验研究常常受到这样一个事实的阻碍，即只能以足够的时间分辨率获得低分辨率的结构数据。分子动力学模拟提供了一种互补的方法，可提供关于折叠过程的极高分辨率的空间和时间数据。目前，此类模拟的有效性受到有关分子动力学力场能否再现蛋白质真实势能面的持续质疑，以及在获得足够的采样以对折叠机制进行有意义的评论方面持续存在的困难的阻碍。我们回顾了蛋白质折叠的三种常见模型系统模拟的最新进展，并讨论了技术和理论上的最新进展如何使蛋白质折叠模拟能够克服其当前的缺点。
相似文献
1
Challenges in protein folding simulations: Timescale, representation, and analysis.蛋白质折叠模拟中的挑战：时间尺度、表示方法和分析
Nat Phys. 2010 Oct 1;6(10):751-758. doi: 10.1038/nphys1713.
2
Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).大分子拥挤现象：化学与物理邂逅生物学（瑞士阿斯科纳，2012年6月10日至14日）
Phys Biol. 2013 Aug;10(4):040301. doi: 10.1088/1478-3975/10/4/040301. Epub 2013 Aug 2.
3
Atomistic molecular simulations of protein folding.蛋白质折叠的原子分子模拟。
Curr Opin Struct Biol. 2012 Feb;22(1):52-61. doi: 10.1016/j.sbi.2011.12.001. Epub 2012 Jan 17.
4
Assessing the accuracy of physical models used in protein-folding simulations: quantitative evidence from long molecular dynamics simulations.评估蛋白质折叠模拟中使用的物理模型的准确性：来自长分子动力学模拟的定量证据。
Curr Opin Struct Biol. 2014 Feb;24:98-105. doi: 10.1016/j.sbi.2013.12.006. Epub 2014 Jan 24.
5
Molecular Dynamics Simulations Are Redefining Our View of Peptides Interacting with Biological Membranes.分子动力学模拟正在重新定义我们对肽与生物膜相互作用的认识。
Acc Chem Res. 2018 May 15;51(5):1106-1116. doi: 10.1021/acs.accounts.7b00613. Epub 2018 Apr 18.
6
Accelerated molecular dynamics simulations of protein folding.蛋白质折叠的加速分子动力学模拟
J Comput Chem. 2015 Jul 30;36(20):1536-49. doi: 10.1002/jcc.23964. Epub 2015 Jun 12.
7
Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure.在二面角能中进行选择性增强采样有助于克服蛋白质折叠中二面角能的增加，并加速寻找蛋白质天然结构。
Phys Chem Chem Phys. 2019 May 22;21(20):10423-10435. doi: 10.1039/c9cp00615j.
8
Machine learning for protein folding and dynamics.机器学习在蛋白质折叠和动力学中的应用。
Curr Opin Struct Biol. 2020 Feb;60:77-84. doi: 10.1016/j.sbi.2019.12.005. Epub 2019 Dec 24.
9
Ultrafast and downhill protein folding.超快且呈下坡式的蛋白质折叠
Curr Opin Struct Biol. 2007 Feb;17(1):38-47. doi: 10.1016/j.sbi.2007.01.001. Epub 2007 Jan 12.
10
Folding free energy landscapes of -sheets with non-polarizable and polarizable CHARMM force fields.无极化和极化 CHARMM 力场下 β-折叠的自由能折叠景观。
J Chem Phys. 2018 Aug 21;149(7):072317. doi: 10.1063/1.5025951.
引用本文的文献
1
2
FINCHES: A Computational Framework for Predicting Intermolecular Interactions in Intrinsically Disordered Proteins.雀类：一种预测内在无序蛋白质分子间相互作用的计算框架。
Int J Mol Sci. 2025 Jun 28;26(13):6246. doi: 10.3390/ijms26136246.
3
GōMartini 3: From large conformational changes in proteins to environmental bias corrections.《戈·马蒂尼3：从蛋白质的大构象变化到环境偏差校正》
Nat Commun. 2025 Apr 30;16(1):4051. doi: 10.1038/s41467-025-58719-0.
4
The Role of Force Fields and Water Models in Protein Folding and Unfolding Dynamics.力场和水模型在蛋白质折叠与去折叠动力学中的作用
J Chem Theory Comput. 2024 Mar 12;20(5):2321-2333. doi: 10.1021/acs.jctc.3c01106. Epub 2024 Feb 19.
5
Molecular Free Energies, Rates, and Mechanisms from Data-Efficient Path Sampling Simulations.基于数据高效路径采样模拟的分子自由能、速率和机制
J Chem Theory Comput. 2023 Dec 26;19(24):9060-9076. doi: 10.1021/acs.jctc.3c00821. Epub 2023 Nov 21.
6
Calculation of Protein Folding Thermodynamics Using Molecular Dynamics Simulations.利用分子动力学模拟计算蛋白质折叠热力学。
J Chem Inf Model. 2023 Dec 25;63(24):7791-7806. doi: 10.1021/acs.jcim.3c01107. Epub 2023 Nov 13.
7
Unveiling Switching Function of Amino Acids in Proteins Using a Machine Learning Approach.利用机器学习方法揭示蛋白质中氨基酸的切换功能。
J Chem Theory Comput. 2023 Nov 28;19(22):8472-8480. doi: 10.1021/acs.jctc.3c00665. Epub 2023 Nov 6.
8
Pathfinder: Protein folding pathway prediction based on conformational sampling.探索者：基于构象采样的蛋白质折叠途径预测。
PLoS Comput Biol. 2023 Sep 11;19(9):e1011438. doi: 10.1371/journal.pcbi.1011438. eCollection 2023 Sep.
9
A Study of a Protein-Folding Machine: Transient Rotation of the Polypeptide Backbone Facilitates Rapid Folding of Protein Domains in All-Atom Molecular Dynamics Simulations.一种蛋白质折叠机器的研究：在全原子分子动力学模拟中，多肽主链的瞬态旋转促进了蛋白质结构域的快速折叠。
Int J Mol Sci. 2023 Jun 13;24(12):10049. doi: 10.3390/ijms241210049.
10
Protein folding mechanism revealed by single-molecule force spectroscopy experiments.单分子力谱实验揭示的蛋白质折叠机制
Biophys Rep. 2021 Oct 31;7(5):399-412. doi: 10.52601/bpr.2021.210024.
本文引用的文献
1
Quantum Chemistry on Graphical Processing Units. 3. Analytical Energy Gradients, Geometry Optimization, and First Principles Molecular Dynamics.图形处理单元上的量子化学。3. 解析能量梯度、几何优化和第一性原理分子动力学。
J Chem Theory Comput. 2009 Oct 13;5(10):2619-28. doi: 10.1021/ct9003004. Epub 2009 Aug 25.
2
Atomic Level Anisotropy in the Electrostatic Modeling of Lone Pairs for a Polarizable Force Field Based on the Classical Drude Oscillator.基于经典德鲁德振荡器的可极化力场中孤对电子静电建模的原子水平各向异性
J Chem Theory Comput. 2006 Nov;2(6):1587-97. doi: 10.1021/ct600180x.
3
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.GROMACS 4：高效、负载均衡和可扩展的分子模拟算法。
J Chem Theory Comput. 2008 Mar;4(3):435-47. doi: 10.1021/ct700301q.
4
ACEMD: Accelerating Biomolecular Dynamics in the Microsecond Time Scale.ACEMD：在微秒时间尺度上加速生物分子动力学
J Chem Theory Comput. 2009 Jun 9;5(6):1632-9. doi: 10.1021/ct9000685. Epub 2009 May 21.
5
All-atom empirical potential for molecular modeling and dynamics studies of proteins.蛋白质分子建模和动力学研究的全原子经验势。
J Phys Chem B. 1998 Apr 30;102(18):3586-616. doi: 10.1021/jp973084f.
6
Polarizable intermolecular potentials for water and benzene interacting with halide and metal ions.水和苯与卤化物及金属离子相互作用的可极化分子间势
J Chem Theory Comput. 2009 Jan 1;5(11):3022-3031. doi: 10.1021/ct9004189.
7
Going beyond clustering in MD trajectory analysis: an application to villin headpiece folding.超越 MD 轨迹分析中的聚类：在 villin 头部折叠中的应用。
PLoS One. 2010 Apr 15;5(4):e9890. doi: 10.1371/journal.pone.0009890.
8
Comparing geometric and kinetic cluster algorithms for molecular simulation data.比较分子模拟数据的几何和动力簇算法。
J Chem Phys. 2010 Feb 21;132(7):074110. doi: 10.1063/1.3301140.
9
A survey of lambda repressor fragments from two-state to downhill folding.从两态到 downhill 折叠的 lambda 阻遏物片段的调查。
J Mol Biol. 2010 Apr 2;397(3):789-98. doi: 10.1016/j.jmb.2010.01.071. Epub 2010 Feb 6.
10
Current status of the AMOEBA polarizable force field.AMOEBA 极化力场的现状。
J Phys Chem B. 2010 Mar 4;114(8):2549-64. doi: 10.1021/jp910674d.
Zotero 插件