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Abstract：
Fullerenes, particularly C60, exhibit unique properties that make them promising candidates for various applications, including drug delivery and nanomedicine. However, their interactions with biomolecules, especially proteins, remain not fully understood. This study implements both explicit and implicit C60 models into the UNRES coarse-grained force field, enabling the investigation of fullerene-protein interactions without the need for restraints to stabilize protein structures. The UNRES force field offers computational efficiency, allowing for longer timescale simulations while maintaining accuracy. Five model proteins were studied: FK506 binding protein, HIV-1 protease, intestinal fatty acid binding protein, PCB-binding protein, and hen egg-white lysozyme. Molecular dynamics simulations were performed with and without C60 to assess protein stability and investigate the impact of fullerene interactions. Analysis of contact probabilities reveals distinct interaction patterns for each protein. FK506 binding protein (1FKF) shows specific binding sites, while intestinal fatty acid binding protein (1ICN) and uteroglobin (1UTR) exhibit more generalized interactions. The explicit C60 model shows good agreement with all-atom simulations in predicting protein flexibility, the position of C60 in the binding pocket, and the estimation of effective binding energies. The integration of explicit and implicit C60 models into the UNRES force field, coupled with recent advances in coarse-grained modeling and multiscale approaches, provides a powerful framework for investigating protein-nanoparticle interactions at biologically relevant scales without the need to use restraints stabilizing the protein, thus allowing for large conformational changes to occur. These computational tools, in synergy with experimental techniques, can aid in understanding the mechanisms and consequences of nanoparticle-biomolecule interactions, guiding the design of nanomaterials for biomedical applications.
摘要：
富勒烯,特别是C60，表现出独特的性能，使它们成为各种应用的有希望的候选者，包括药物输送和纳米医学。然而,它们与生物分子的相互作用，尤其是蛋白质，仍然没有完全理解。本研究将显式和隐式C60模型实现到UNRES粗粒度力场中，能够研究富勒烯-蛋白质相互作用，而不需要限制来稳定蛋白质结构。UNRES力场提供了计算效率，允许更长的时间尺度模拟，同时保持准确性。研究了五种模型蛋白：FK506结合蛋白，HIV-1蛋白酶,肠脂肪酸结合蛋白，PCB结合蛋白，和鸡蛋白溶菌酶。在有和没有C60的情况下进行分子动力学模拟以评估蛋白质稳定性并研究富勒烯相互作用的影响。接触概率的分析揭示了每种蛋白质的不同相互作用模式。FK506结合蛋白(1FKF)显示特异性结合位点,而肠道脂肪酸结合蛋白（1ICN）和子宫血红蛋白（1UTR）表现出更广泛的相互作用。显式C60模型在预测蛋白质灵活性方面与全原子模拟显示出良好的一致性，C60在装订袋中的位置，以及有效结合能的估计。将显式和隐式C60模型集成到UNRES力场中，再加上粗粒度建模和多尺度方法的最新进展，提供了一个强大的框架，用于在生物相关尺度上研究蛋白质-纳米颗粒相互作用，而无需使用稳定蛋白质的约束，从而允许发生大的构象变化。这些计算工具，与实验技术协同，可以帮助理解纳米颗粒-生物分子相互作用的机制和后果，指导生物医学应用纳米材料的设计。
