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Affinity of HIV-1 antibody 2G12 with monosaccharides: A theoretical study based on explicit and implicit water models

Paper ID Volume ID Publish Year Pages File Format Full-Text
15074 1371 2014 9 PDF Available
Title
Affinity of HIV-1 antibody 2G12 with monosaccharides: A theoretical study based on explicit and implicit water models
Abstract

•Affinities of HIV-1 antibody 2G12 with monosaccharides were examined.•QM methods with explicit and implicit water models were applied.•d-Fructose's higher binding affinity over d-mannose was clarified.•Stronger binding of d-fructose over d-mannose was due to the solvation effects.•Significant pair interactions among d-fructose, amino acids, and waters were found.

In order to develop potential ligands to HIV-1 antibody 2G12 toward HIV-1 vaccine, binding mechanisms of the antibody 2G12 with the glycan ligand of d-mannose and d-fructose were theoretically examined. d-Fructose, whose molecular structure is slightly different from d-mannose, has experimentally shown to have stronger binding affinity to the antibody than that of d-mannose. To clarify the nature of d-fructose's higher binding affinity over d-mannose, we studied interaction between the monosaccharides and the antibody using ab initio fragment molecular orbital (FMO) method considering solvation effect as implicit model (FMO-PCM) as well as explicit water model. The calculated binding free energies of the glycans were qualitatively well consistent with the experimentally reported order of their affinities with the antibody 2G12. In addition, the FMO-PCM calculation elucidated the advantages of d-fructose over d-mannose in the solvation energy as well as the entropic contribution term obtained by MD simulations. The effects of explicit water molecules observed in the X-ray crystal structure were also scrutinized by means of FMO methods. Significant pair interaction energies among d-fructose, amino acids, and water molecules were uncovered, which indicated contributions from the water molecules to the strong binding ability of d-fructose to the antibody 2G12. These FMO calculation results of explicit water model as well as implicit water model indicated that the strong binding of d-fructose over d-mannose was due to the solvation effects on the d-fructose interaction energy.

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Keywords
HIV-1 antibody 2G12; d-Mannose and d-fructose; FMO-PCM; In silico ligand structure; Solvation effect; Binding free energy
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Affinity of HIV-1 antibody 2G12 with monosaccharides: A theoretical study based on explicit and implicit water models
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 49, April 2014, Pages 36–44
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us