L-Asparaginase II (asnB), a periplasmic protein, commercially extracted from E. coli and Erwinia, is often used to treat Acute Lymphoblastic Leukemia. L-Asparaginase is an enzyme that converts L-asparagine to aspartic acid and ammonia. Cancer cells are dependent on asparagine from other sources for growth and when these cells are deprived of asparagine by the action of the enzyme the cancer cells selectively die. Questions remain as to whether asnB from E. coli and Erwinia is the best asparaginase as they have many side-effects. asnB with the lowest Michaelis constant (Km) (most potent), and with the lowest immunogenicity is considered the most optimal enzyme. In this paper asnB sequence of E. coli was used to search for homologous proteins in different bacterial and archaeal phyla and a maximum likelihood phylogenetic tree was constructed. The sequences that are most distant from E. coli and Erwinia were considered best candidates in terms of immunogenicity and were chosen for further processing. The structures of these proteins were built by homology modeling and asparagine was docked with these proteins to calculate the binding energy. asnBs from Streptomyces griseus, Streptomyces venezuelae and Streptomyces collinus were found to have the highest binding energy i.e. -5.3 kcal/mol, -5.2 kcal/mol, and -5.3 kcal/mol respectively (Higher than the E.coli and Erwinia asnBs) and were predicted to have the lowest Kms as we found that there is an inverse relationship between binding energy and Km. Besides predicting the most optimal asparaginase, this technique can also be used to predict the most optimal enzymes where the substrate is known and the structure of one of the homologs is solved.

中文翻译：

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计算机上开发使用抗急性淋巴细胞白血病的L-天冬酰胺酶II选择最佳酶的方法。

L-天冬酰胺酶II（asnB）是一种周质蛋白，可从大肠杆菌和欧文氏菌中商业提取，通常用于治疗急性淋巴细胞白血病。L-天冬酰胺酶是将L-天冬酰胺转化为天冬氨酸和氨的酶。癌细胞依赖于其他来源的天冬酰胺生长，并且当这些细胞通过酶的作用而被剥夺天冬酰胺时，癌细胞选择性地死亡。对于来自大肠杆菌和欧文氏菌的asnB是否具有最佳副作用，仍存在疑问。具有最低米氏常数（Km）（最有效）且具有最低免疫原性的asnB被认为是最佳酶。本文利用大肠杆菌的asnB序列搜索不同细菌和古细菌门的同源蛋白，并构建了最大似然系统树。就免疫原性而言，与大肠杆菌和欧文氏菌最远的序列被认为是最佳候选，并被选择进行进一步加工。这些蛋白质的结构通过同源性建模建立，天冬酰胺与这些蛋白质对接以计算结合能。发现来自灰链霉菌，委内链霉菌和链霉菌的asnB具有最高的结合能，分别为-5.3 kcal / mol，-5.2 kcal / mol和-5.3 kcal / mol（高于大肠杆菌和欧文氏菌asnBs）和由于我们发现结合能和Km之间存在反比关系，因此预测Kms最低。除了预测最理想的天冬酰胺酶，