We’re always happy at the lab when a student defends their dissertation thesis and now it was the turn of Raúl Márquez-Avilés to do so with flying colors.

The title of his dissertation is “Molecular Dynamics Simulations of 5 potential entry inhibitors for HIV-1“. He performed 500 ns long molecular dynamics simulations of the CD4 – gp 120 proteins interacting with one or several molecules of various lead compounds with inhibitory properties. The leads were obtained previously in our group (by Durbis Castillo, now at McGill) from a massive docking library of ca. 16 million compounds, all having a central piperazine core (Fig1)

Figure 1. Lead compounds: Piperazine cores with heterocyclic substitutions.

The protein gp120 is a surface glyco-protein located at the surface of the HIV virus which couples to the CD4 protein on lymphocytes-T, being this the first step in the infection process of a healthy cell; generating inhibitors of this coupling could help stop the infection from spreading systemically. Four systems were devised: (SB) The reference state for which only gp-120 and CD4 were considered, (S2) A single ligand molecule was placed in the Phe43 cavity of gp120 to assess their inhibitory capacity, (S3) the ligand was placed right outside the Phe43 cavity to assess their entry capacity, and (S4) five ligand molecules were placed outside the Phe43 cavity of gp120 to force their entry (Fig2). Their binding energies were calculated using MM-PBSA and although all five ligands show statistically similar results as inhibitors all five exhibit a stronger binding energy than the reference proving their efficacy in preventing the coupling of the virus to the healthy cell. As a bonus, his research on system S4 shed light on the existence of an allosteric site on gp120 that will warrant further research in our group.

Figure 2. Systems for which 500 ns MD simulations were performed.

This work is still pending publication.

Raúl Márquez has always proven to be a hard working person who is also very self-sufficient student, a very cheerful labmate, and, as I just learned yesterday, an avid chess player. I’m sure he has a bright future in whichever endeavor he chooses now. Congratulations Raúl Márquez-Avilés!

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