Force-field development and molecular dynamics simulations of ferrocene-peptide conjugates as a scaffold for hydrogenase mimics.
Force-field development and molecular dynamics simulations of ferrocene-peptide conjugates as a scaffold for hydrogenase mimics.
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作为氢化酶模拟物支架的二茂铁-肽缀合物的力场开发和分子动力学模拟。
DOI：
10.1002/chem.200700358
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
N. Metzler‐Nolte
中科院分区：
文献类型：
--
作者：
Xavier de Hatten;Z. Cournia;I. Huc;Jeremy C. Smith;N. Metzler‐Nolte
氢化酶在新能源研究领域中的重要性日益增加，促使我们利用分子动力学 (MD) 模拟，基于二茂铁肽支架，研究潜在氢化酶模拟物的结构和动力学。为了实现这项 MD 研究，在 CHARMM 模拟软件包中开发并实施了含二茂铁肽的分子力学力场，从而将该软件包的用途扩展到肽-生物有机金属化学。使用自动频率匹配方法（AFMM），通过量子化学参考正常模式生成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拟合到量子化学计算的静电势而得出的。针对二茂铁-1,1'-二羧酸二肽衍生物的实验X射线晶体结构测试了力场。计算准确地再现了分子几何形状，包括特征性 C2 对称分子内氢键模式，该模式在 0.1 微米 MD 模拟中保持稳定。二茂铁-1-(D)丙氨酸-(D)脯氨酸-1'-(D)丙氨酸-(D)脯氨酸的晶体堆积特性也被准确再现。该晶体的晶格参数在 0.1 微米 MD 模拟过程中保持不变，并且与实验值几乎完全匹配。肽在二氯甲烷中的模拟也与溶液中的实验 NMR 和圆二色性 (CD) 数据非常一致。开发的力场用于对 [Ni-Fe] 氢化酶活性位点周围的新型尚未合成的肽片段进行 MD 模拟。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。因此，所提出的茂金属 MD 模拟结果为我们使用二茂铁肽作为最小酶模拟物的建议提供了令人信服的验证。
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 point charges to quantum-chemically computed electrostatic potentials. The force field was tested against experimental X-ray crystal structures of dipeptide derivatives of ferrocene-1,1'-dicarboxylic acid. The calculations reproduce accurately the molecular geometries, including the characteristic C2-symmetrical intramolecular hydrogen-bonding pattern, that were stable over 0.1 micros MD simulations. The crystal packing properties of ferrocene-1-(D)alanine-(D)proline-1'-(D)alanine-(D)proline were also accurately reproduced. The lattice parameters of this crystal were conserved during a 0.1 micros MD simulation and match the experimental values almost exactly. Simulations of the peptides in dichloromethane 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-peptides as minimal enzyme mimics.
来自 Desulfovibrio gigas 的 [NiFe] 氢化酶的活性位点。
DOI：
--
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huynh,BH;Patil,DS;Moura,I;Teixeira,M;Moura,JJ;DerVartanian,DV;Czechowski,MH;Prickril,BC;PeckJr,HD;LeGall,J
通讯作者：
LeGall,J
影响因子：
15
作者：
Feller, SE;Gawrisch, K;MacKerell, AD
通讯作者：
MacKerell, AD
影响因子：
15
作者：
Scott, JD;Williams, RM
通讯作者：
Williams, RM