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:

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.

MM parameters for the following covalent complexes resulting from inhibition with clavulanate are present:

AEC - acyl-enzyme complex of clavulanate (incl. Ser70)

Files: AEC.off, AEC.frcmod

Residue name: AEC

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]

Files: TEDC.off, TEDC.frcmod

Residue name: TDC

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

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.

[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.