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Insight into the modified Ibalizumab–human CD4 receptor interactions: using a computational binding free energy approach

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Abstract

Antibody drugs are very useful tools for the treatment of many chronic diseases. Recently, however, patients and doctors have encountered the problem of drug resistance. How to improve the affinity of antibody drugs has therefore become a pressing issue. Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary receptor for human immunodeficiency virus type 1. This study investigates the mutation residues of the complementarity determining regions of Ibalizumab. We propose using the wild and mutations of Ibalizumab–human CD4 receptor complex structures, molecular dynamics techniques, alanine-scanning mutagenesis calculations and solvated interaction energies methods to predict the binding free energy of the Ibalizumab–human CD4 receptor complex structures. This work found that revealed three key positions (31th, 32th and 33th in HCDR-1) of the residues may play an important role in Ibalizumab–human CD4 receptor complex interactions. Therefore, bioengineering substitutions of the three key positions and increasing number of intermolecular interactions (HCDR-1 of Ibalizumab/human CD4 receptor) might improve the binding affinities of this complex structure.

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Acknowledgments

The authors would like to thank the Kaohsiung Medical University of the Republic of China and the National Science Council of the Republic of China, Taiwan, for supporting this research (Contract No. NSC 101-2113-M-492-001-MY2, KMU-Q103012 and KMU-TP103C00).

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Yeng-Tseng Wang & Lea-Yea Chuang

  2. Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yeng-Tseng Wang

Authors
  1. Yeng-Tseng Wang
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  2. Lea-Yea Chuang
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Correspondence to Yeng-Tseng Wang.

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Wang, YT., Chuang, LY. Insight into the modified Ibalizumab–human CD4 receptor interactions: using a computational binding free energy approach. J Comput Aided Mol Des 29, 69–78 (2015). https://doi.org/10.1007/s10822-014-9805-4

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  • DOI: https://doi.org/10.1007/s10822-014-9805-4

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