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

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Schiffer Lab

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biochemistry | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Pharmaceutics and Drug Design | Structural Biology


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.


Crystal structures, Drug design, HIV-1, Inhibitor, MD, NMR, Protease

DOI of Published Version



J Biomol NMR. 2019 Jul;73(6-7):365-374. doi: 10.1007/s10858-019-00260-6. Epub 2019 Jun 26. Link to article on publisher's site

Journal/Book/Conference Title

Journal of biomolecular NMR

Related Resources

Link to Article in PubMed

PubMed ID