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Journal of Biomolecular NMR

, Volume 73, Issue 6–7, pp 365–374 | Cite as

NMR and MD studies combined to elucidate inhibitor and water interactions of HIV-1 protease and their modulations with resistance mutations

  • Rieko Ishima
  • Nese Kurt Yilmaz
  • Celia A. SchifferEmail author
Article
  • 96 Downloads

Abstract

Over the last two decades, both the sensitivity of NMR and the time scale of molecular dynamics (MD) simulation have increased tremendously and have advanced the field of protein dynamics. HIV-1 protease has been extensively studied using these two methods, and has presented a framework for cross-evaluation of structural ensembles and internal dynamics by integrating the two methods. Here, we review studies from our laboratories over the last several years, to understand the mechanistic basis of protease drug-resistance mutations and inhibitor responses, using NMR and crystal structure-based parallel MD simulations. Our studies demonstrate that NMR relaxation experiments, together with crystal structures and MD simulations, significantly contributed to the current understanding of structural/dynamic changes due to HIV-1 protease drug resistance mutations.

Keywords

Drug design HIV-1 Protease Inhibitor NMR MD Crystal structures 

Notes

Acknowledgements

We thank Teresa Brosenitsch for critical reading of the manuscript. This study was supported by Grants from the National Institutes of Health (P01 GM109767).

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Authors and Affiliations

  1. 1.Department of Structural BiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of Biochemistry and Molecular PharmacologyUniversity of Massachusetts Medical SchoolWorcesterUSA

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