In Silico Molecular Docking Study for Prediction of Binding Affinities to Penicillin Binding Proteins and β-Lactamases of Amino Acids-Cephalexin conjugates


  • Shakir Mahmood Alwan Department of Pharmacy, Al-Farabi University College, Baghdad, Iraq
  • Jaafar S. Shia Department of Pharmacy, Al-Farabi University College, Baghdad, Iraq



Cephalexin, Amino acids, Molecular docking, PBPs, β-lactamases, Molinspiration calculations, drug-likeness


Cephalexin is a first generation cephalosporin with high antibacterial activity against a number of microbes. Cephalexin is highly sensitive and could be hydrolyzed by almost all of β-lactamases. An in silico prediction and evaluation study is performed to find a possibility of bringing new life to cephalexin, and other cephalosporins that are susceptible to hydrolysis by lactamases. This approach includes an introduction of an amino acid moiety into cephalexin through an amide bond with its primary amine group. This amino acid moiety is expected to provide steric hindrance and protecting the β-lactam ring from being hydrolyzed. In silico study included measurement of binding affinity to penicillin binding proteins (PBPs) and D-alanyl-D-alanine carboxypeptidases and to β-lactamases. Drug likeness and Molinspiration calculations were recorded to find a reliable correlation with better activity and stability against β-lactamases. The newly suggested conjugates that recorded the best score of binding affinity on PBPs are L-Phe-Cephalexin, L-Arg-Cephalexin, L-Tyr-Cephalexin and L-Thr-Cephalexin. Two of these conjugates, namely, L-Arg-Cephalexin and L-Tyr-Cephalexin recorded high binding affinity scores on D-alanyl-D-alanine carboxypeptidases. Moreover, the predicted stability of L-Arg-Cephalexin and L-Tyr-Cephalexin conjugates against β-lactamases was recorded. Drug-Likeness parameters have shown that L-Cys-Cephalexin, L-Lys-Cephalexin and L-Arg-Cephalexin conjugates were the best compounds recording the highest binding affinity. In conclusion, the amino acid-linked cephalexin conjugates were found to possess high binding affinity to PBPs, D-alanyl-D-alanine carboxypeptidases and β-lactamases, which may encourage the synthesis and intensive evaluation.


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