Cell Biochemistry and Biophysics

, Volume 44, Issue 3, pp 395–404 | Cite as

Molecular dynamics simulations applied to the study of subtypes of HIV-1 protease common to Brazil, Africa, and Asia

  • Paulo R. Batista
  • Alan Wilter
  • Elza H. A. B. Durham
  • Pedro G. Pascutti
Original Article


Africa accounts for the majority of HIV-1 infections worldwide caused mainly by the A and C viral subtypes rather than B subtype, which prevails in the United States and Western Europe. In Brazil, B subtype is the major subtype, but F, C, and A also circulate. These non-B subtypes present polymorphisms, and some of them occur at sites that have been associated with drug resistance, including the HIV-1 protease (PR), one important drug target. Here, we report a Molecular Dynamics study of the B and non-B PR complexed with the inhibitor ritonavir to delineate the behavior of each subtype. We compare root mean squared deviation, binding free energy by linear interaction energy approach, hydrogen bonds, and intermolecular contact surface area between inhibitor and PR. From our results, we can provide a basis to understand the molecular mechanism of drug resistance in non-B subtypes. In this sense, we found a decrease of approx 4 kcal/mol in ΔG of binding between B and non-B subtypes. This corresponds to the loss of one hydrogen bond, which is in agreement with our H-bond analysis. Previous experimental affinity studies reported analogous results with inhibition constant values for non-B PR.

Index Entries

Molecular Dynamics Gromacs HIV-1 protease ritonavir subtypes non-B modelling free energy LIE 


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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Paulo R. Batista
    • 1
    • 4
  • Alan Wilter
    • 2
    • 4
  • Elza H. A. B. Durham
    • 3
    • 4
  • Pedro G. Pascutti
    • 1
    • 4
  1. 1.Laboratório de Modelagem e Dinâmica Molecular, Instituto de Biofisica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Laboratório Nacional de Computação CientificaRio de JaneiroBrazil
  3. 3.Instituoo Ludwig de Pesquisa sobre o CâncerSão PauloBrazil
  4. 4.Instituto de Matemática e EstatisticaUniversidade São PauloSão PauloBrazil

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