Analysis of enzymatic processes using linear-scaling quantum-chemical methods (C07)

该项目的主要目标是使用线性尺度量子化学(QM)和QM/MM(QM/分子力学)方法来研究活跃的DNA去甲基化背后的机制，这种去甲基化在基因表达和干细胞分化中起着基础作用。通过QM/MM计算，我们旨在了解参与处理表观修饰的DNA碱基的酶的结合亲和力和催化活性。这里，线性标度技术允许对1000多个原子进行精确的电子处理，以描述这类酶的催化中心。该项目的另一个部分是利用量子化学研究来开发作为酶活性部位的亲电分子的分子的反应性标度。在这里，最终目标是设计有效的、不可逆转地结合的抗生素。

The main goal of the project is to employ linear-scaling quantum-chemical (QM) and QM/MM (QM/ molecular mechanical) methods for studying the mechanisms behind active DNA demethylation that plays a fundamental role in gene expression and the differentiation of stem cells.With the QM/MM calculations we aim for an understanding of the binding affinities and catalytic activities of enzymes that are involved in processing epigenitically modified DNA bases.Here, the linear-scaling techniques allow for an accurate electronic treatment of more than 1000 atoms for describing the catalytic center of such enzymes.Another part of the project is to use quantum chemical investigations for developing a reactivity scale for molecules as electrophiles in the active site of enzymes. Here, the ultimate goal is to design effective, irreversibly binding antibiotics.