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首页> 外文期刊>Chemistry: A European journal >Force-Field Development and Molecular Dynamics Simulations of Ferrocene-Peptide Conjugates as a Scaffold for Hydrogenase Mimics
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Force-Field Development and Molecular Dynamics Simulations of Ferrocene-Peptide Conjugates as a Scaffold for Hydrogenase Mimics

机译：二茂铁-肽共轭物作为氢酶模拟物的支架的力场发展和分子动力学模拟。

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The increasing importance of hydrogenase enzymes in the new energy research field has led us to examine the structure and dynamics of potential hydrogenase mimics, based on a ferrocene-peptide scaffold, using molecular dynamics (MD) simulations. To enable this MD study, a molecular mechanics force field for ferrocene-bearing peptides was developed and implemented in the CHARMM simulation package, thus extending the usefulness of the package into peptide-bioorganometallic chemistry. Using the automated frequency-matching method (AFMM), optimized intramolecular force-field parameters were generated through quantum chemical reference normal modes. The partial charges for ferrocene were derived by fitting pointcharges to quantum-chemically computed electrostatic potentials. The force field was tested against experimental X-ray crystal structures of di-peptide derivatives of ferrocene-1,1'-dicarboxylic acid. The calculations reproduce accurately the molecular geometries, including the characteristic C_2-symmetrical intramolecular hydrogen-bonding pattern, that were stable over 0.1 mu s MD simulations. The crystal packing properties of ferrocene-1-(D)alanine-(D)proline-T-(D)alanine-(D)proline were also accurately reproduced. The lattice parameters of this crystal were conserved during a 0.1 mu s MD simulation and match the experimental values almost exactly. Simulations of the peptides in dichloro-methane are also in good agreement with experimental NMR and circular dichroism (CD) data in solution. The developed force field was used to perform MD simulations on novel, as yet unsynthesized peptide fragments that surround the active site of [Ni-Fe] hydrogenase. The results of this simulation lead us to propose an improved design for synthetic peptide-based hydrogenase models. The presented MD simulation results of metallocenes thereby provide a convincing validation of our proposal to use ferrocene-pep-tides as minimal enzyme mimics.
机译：氢化酶在新能源研究领域的重要性日益提高，已使我们使用分子动力学（MD）模拟技术，基于二茂铁-肽支架，研究了潜在的氢化酶模拟物的结构和动力学。为了进行此MD研究，在CHARMM模拟程序包中开发并实现了含二茂铁的肽的分子力学力场，从而将程序包的用途扩展到了肽-生物有机金属化学中。使用自动频率匹配方法（AFMM），通过量子化学参考标准模式生成了优化的分子内力场参数。二茂铁的部分电荷是通过将点电荷与量子化学计算的静电势拟合而得出的。针对二茂铁-1，1′-二羧酸的二肽衍生物的实验X射线晶体结构测试了力场。计算结果准确地再现了分子几何结构，包括特征性的C_2对称分子内氢键模式，在0.1 s s的MD模拟下保持稳定。还精确地再现了二茂铁-1-（D）丙氨酸-（D）脯氨酸-T-（D）丙氨酸-（D）脯氨酸的晶体堆积特性。该晶体的晶格参数在0.1 s s MD模拟期间得以保留，并且几乎与实验值完全匹配。在二氯甲烷中模拟肽段与溶液中的实验NMR和圆二色性（CD）数据也非常吻合。发达的力场被用于对新型的尚未合成的肽片段进行MD模拟，这些肽片段围绕[Ni-Fe]氢化酶的活性位点。该模拟的结果使我们提出了基于合成肽的氢化酶模型的改进设计。提出的茂金属的MD模拟结果从而提供了令人信服的验证，证明了我们建议使用二茂铁-二肽作为最小的酶模拟物。

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