DFT CALCULATIONS FOR VITAMIN B12 COMPOUNDS AND REACTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 含有维生素B12的酶，蛋氨酸合成酶，是人体中位于必需代谢途径中的最重要的酶之一。维生素B12化合物，称为钴，这是钴-咕啉环系统的分子轨道计算，是要了解他们的化学和生物化学性质。我们比较了完整的甲钴胺结构（183个原子，506个电子）的PM 3半经验方法与在B3 LYP/LANL 2DZ水平上的CH 3-咕啉Im（咪唑）（73个原子，274个电子）的模型系统的DFT计算。虽然PM 3的几何形状接近于DFT计算的几何形状，但很明显，能量和分子轨道轮廓对于PM 3的结果甚至在定性上都不正确。文献中先前的DFT模型计算都不是用带负电荷的含磷酸根的侧链进行的，这将改变分子上的总电荷。我们以前的大多数DFT计算都是在单节点计算机上使用高斯（98或03）程序进行的，对模型化合物进行一次几何优化可能需要两周以上的时间（418个基函数，1097个原始高斯）。我们现在需要对更完整的模型钴胺素系统进行DFT计算，这将需要多处理器计算和大量内存，以便正确模拟烷基钴胺素、NO-钴胺素、N2 O-钴胺素和其他物质的几何形状和键离解能，以及拉曼光谱、还原电位，以及酶促反应和化学反应中的过渡态，其中Co-C键和NO-Co键断裂。这些研究应有助于了解蛋氨酸合成酶的活性位点的机制，它使用甲钴胺作为辅助因子。计算将涉及精确的溶剂化计算和最终的甲硫氨酸合酶的甲钴胺活性位点的QM/MM。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The vitamin B12 containing enzyme , methionine synthase, is one of the most important enzymes in the human body situated in essential metabolic pathways. Molecular orbital calculations on vitamin B12 compounds, called cobalamins , which are cobalt -corrin ring systems, are to be made to understand their chemical and biochemical properties. We have compared the PM3 semi-empirical method for the complete methylcobalamin structure ( 183 atoms, 506 electrons) with a DFT calculations at the B3LYP/LANL2DZ level for a model system of CH3-corrin Im (imidazole) (73 atoms, 274 electrons). Although PM3 geometry is close to that of the DFT calculations, it is clear that energies and molecular orbital contours are not even qualitatively correct for PM3 results. None of the previous DFT model calculations in the literature were made with the negatively charged phosphate containing side chain which would change the overall charge on the molecules. Most of our previous DFT calculations were made with the Gaussian ( 98 or 03) program on a single node computer and a single geometric optimization of the model compound could take more than two weeks ( 418 basis functions, 1097 primitive Gaussians). We now need to make DFT calculations on more complete model cobalamin systems which will require multiprocessor calculations and large amounts of memory , in order to correctly model geometry and bond dissociation energies of alkyl-cobalamins, NO-cobalamin, N2O-cobalamin , and other species, and Raman spectra, reduction potentials, and transition states in the enzymatic reactions and chemical reactions where the Co-C bond and NO-Co bonds are broken. These studies should help in understanding mechanisms at the active site of methionine synthase which uses methylcobalamin as a cofactor. Calculations will involve accurate solvation calculations and eventually QM/MM of the methylcobalamin active site of methionine synthase.