MM parameters for covalent adducts of Clavulanate degradation by beta-lactamases

This dataset contains parameters for the acyl-enzyme complexes simulated in the following work:<br>Multiscale simulations establish clavulanate inhibition efficiency and the responsible enzyme complex in class A β-lactamases. [1]Rubén A. Fritz, Jans H. Alzate-Morales, James Spencer, Adrian J. Mulholland and Marc W. Van der Kamp. <br>MM parameters for the following covalent complexes resulting from inhibition with clavulanate are present: <br>AEC - acyl-enzyme complex of clavulanate (incl. Ser70) Files: AEC.off, AEC.frcmod Residue name: AEC <br>TEDC - decarboxylated trans-enamine complex (incl. Ser70) that is the result of opening of the five-membered ring (leading to an imine intermediate) and subsequent rearrangement [2,3] <br>Files: TEDC.off, TEDC.frcmod Residue name: TDC<br>ADEC - aldehyde complex (incl. Ser70) that is the result of consecutive reactions of the cis-enamine [2,3] Files: ADEC.off, ADEC.frcmod Residue name: ADC <br>Parameterisation procedure: Initial Amber ff14SB force field parameters for the acylated residue in the models (adducts) were obtained from the RED Server (partial charges from HF/6-31G(d,p) RESP-fitting and atom types). For missing parameters, chemically equivalent parameters from the GAFF force field were used. <br>[1] Fritz RA, Alzate-Morales JH, Spencer J, Mulholland AJ and Van der Kamp MW. Biochemistry (2018). Under review.[2] Drawz, S. M., and Bonomo, R. a. (2010) Three decades of β-lactamase inhibitors. Clin. Microbiol. Rev. 23, 160–201. [3] Helfand, M. S., Totir, M. A., Carey, M. P., Hujer, A. M., Bonomo, R. A., and Carey, P. R. (2003) Following the Reactions of Mechanism-Based Inhibitors with β-Lactamase by Raman Crystallography. Biochemistry 42, 13386–13392.

本数据集收录了下述研究中模拟的酰基酶复合物相关参数：<br>《多尺度模拟确立克拉维酸（clavulanate）的抑制效率及其在A类β-内酰胺酶（class A β-lactamases）中的关键作用酶复合物》[1]，作者为Rubén A. Fritz、Jans H. Alzate-Morales、James Spencer、Adrian J. Mulholland及Marc W. Van der Kamp。<br><br>本数据集包含以下由克拉维酸抑制产生的共价复合物的分子力学（Molecular Mechanics, MM）参数：<br>AEC——克拉维酸来源的酰基酶复合物（acyl-enzyme complex，包含Ser70活性位点），配套文件为AEC.off、AEC.frcmod，残基命名为AEC；<br>TEDC——脱羧反式烯胺复合物（decarboxylated trans-enamine complex，包含Ser70活性位点），为五元环开环（生成亚胺中间体）并经后续重排得到的产物[2,3]，配套文件为TEDC.off、TEDC.frcmod，残基命名为TDC；<br>ADEC——醛复合物（aldehyde complex，包含Ser70活性位点），为顺式烯胺发生连续反应的产物[2,3]，配套文件为ADEC.off、ADEC.frcmod，残基命名为ADC。<br><br>参数化流程如下：模型中酰化残基（加合物）的初始Amber ff14SB力场（Amber ff14SB force field）参数通过RED服务器（RED Server）获取，其部分电荷来自HF/6-31G(d,p)水平下的RESP拟合（RESP-fitting）与原子类型分配。对于缺失的参数，采用GAFF力场（GAFF force field）中化学等价的参数进行补充。<br><br>参考文献：<br>[1] Fritz RA, Alzate-Morales JH, Spencer J, Mulholland AJ 及 Van der Kamp MW. 《Biochemistry》(2018). 正在审稿中。<br>[2] Drawz SM, Bonomo RA. (2010) 三十年β-内酰胺酶抑制剂研究. 《临床微生物学综述》, 23, 160–201.<br>[3] Helfand MS, Totir MA, Carey MP, Hujer AM, Bonomo RA, Carey PR. (2003) 利用拉曼晶体学追踪机制性抑制剂与β-内酰胺酶的反应过程. 《生物化学》, 42, 13386–13392.