Biomaterial Database

Quantum computational analysis for drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations. 2005

Xiao He, and Ye Mei, and Yun Xiang, and Da W Zhang, and John Z H Zhang

Department of Chemistry, Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of Ministry of Education (MOE), Nanjing University, Nanjing 210093, People's Republic of China.

Quantum chemical calculation has been carried out to analyze binding interactions of nevirapine to HIV-1 reverse transcriptase (RT) and single point mutants Lys103 --> Asn (K103N) and Tyr181--> Cys (Y181C). In this study, the entire system of HIV-1 RT/nevirapine complex with over 15,000 atoms is explicitly treated by using a recently developed MFCC (molecular fractionation with conjugate caps) approach. Quantum calculation of protein-drug interaction energy is performed at Hartree-Fock and DFT levels. The RT-nevirapine interaction energies are computed at fixed geometries given by the crystal structures of the HIV-1 RT/nevirapine complexes from protein data bank (PDB). The present calculation provides a quantum mechanical interaction spectrum that explicitly shows interaction energies between nevirapine and individual amino-acid fragments of RT. Detailed interactions that are responsible for drug resistance of two major RT mutations are elucidated based on computational analysis in relation to the crystal structures of binding complexes. The present result provides a qualitative molecular understanding of HIV-1 RT drug resistance to nevirapine and gives useful guidance in designing improved inhibitors with better resistance to RT mutation.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D011789	Quantum Theory	The theory that the radiation and absorption of energy take place in definite quantities called quanta (E) which vary in size and are defined by the equation E	Quantum Theories,Theories, Quantum,Theory, Quantum
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D017354	Point Mutation	A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.	Mutation, Point,Mutations, Point,Point Mutations
D054303	HIV Reverse Transcriptase	A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.	Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D018894	Reverse Transcriptase Inhibitors	Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.	Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse
D019295	Computational Biology	A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.	Bioinformatics,Molecular Biology, Computational,Bio-Informatics,Biology, Computational,Computational Molecular Biology,Bio Informatics,Bio-Informatic,Bioinformatic,Biologies, Computational Molecular,Biology, Computational Molecular,Computational Molecular Biologies,Molecular Biologies, Computational
D019380	Anti-HIV Agents	Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.	AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D019829	Nevirapine	A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.	BI-RG-587,Nevirapine Hemihydrate,Viramune,BI RG 587,BIRG587,Hemihydrate, Nevirapine