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Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

Saurabh, Suman and Sahoo, Anil Kumar and Maiti, Prabal K (2016) Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor. In: 27th IUPAP Conference on Computational Physics (CCP), DEC 02-05, 2015, Guwahati, INDIA.

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Official URL: http://dx.doi.org/10.1088/1742-6596/759/1/012020

Abstract

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

Item Type: Conference Proceedings
Additional Information: Copy right for this article belongs to the IOP PUBLISHING LTD, DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
Department/Centre: Division of Physical & Mathematical Sciences > Physics
Depositing User: Id for Latest eprints
Date Deposited: 09 Feb 2017 07:03
Last Modified: 09 Feb 2017 07:03
URI: http://eprints.iisc.ac.in/id/eprint/56233

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