BIOMAT Database Logo BIOMAT Database Logo

All-atom models for the non-nucleoside binding site of HIV-1 reverse transcriptase complexed with inhibitors: a 3D QSAR approach. 1996

R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Frederick Biomedical Supercomputing Center, National Cancer Institute-FCRDC, Frederick, Maryland 21702, USA.

Several molecular modeling techniques were used to generate an all-atom molecular model of a receptor binding site starting only from Ca atom coordinates. The model consists of 48 noncontiguous residues of the non-nucleoside binding site of HIV-1 reverse transcriptase and was generated using a congeneric series of nevirapine analogs as structural probes. On the basis of the receptor-ligand atom contacts, the program HINT was used to develop a 3D quantitative structure activity relationship that predicted the rank order of binding affinities for the series of inhibitors. Electronic profiles of the ligands in their docked conformations were characterized using electrostatic potential maps and frontier orbital calculations. These results led to the development of a 3D stereoelectronic pharmacophore which was used to construct 3D queries for database searches. A search of the National Cancer Institute's open database identified a lead compound that exhibited moderate antiviral activity.

UI MeSH Term Description Entries
D007256 Information Systems Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. Ancillary Information Systems,Emergency Care Information Systems,Information Retrieval Systems,Perinatal Information System,Ancillary Information System,Information Retrieval System,Information System,Information System, Ancillary,Information System, Perinatal,Perinatal Information Systems,Systems, Information Retrieval
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
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
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
D012194 RNA-Directed DNA Polymerase An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49. DNA Polymerase, RNA-Directed,RNA-Dependent DNA Polymerase,Reverse Transcriptase,RNA Transcriptase,Revertase,DNA Polymerase, RNA Directed,DNA Polymerase, RNA-Dependent,RNA Dependent DNA Polymerase,RNA Directed DNA Polymerase
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
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

Related Publications

R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
QSAR for non-nucleoside inhibitors of HIV-1 reverse transcriptase.
September 2006, Bioorganic & medicinal chemistry,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Comparative study of non nucleoside inhibitors with HIV-1 reverse transcriptase based on 3D-QSAR and docking.
January 2003, SAR and QSAR in environmental research,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Receptor- and ligand-based 3D-QSAR study for a series of non-nucleoside HIV-1 reverse transcriptase inhibitors.
March 2009, Bioorganic & medicinal chemistry,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
The QSAR analysis of tricyclic non-nucleoside inhibitors of HIV-1 reverse transcriptase.
January 2003, Acta poloniae pharmaceutica,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
3D-QSAR CoMFA of a series of DABO derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors.
August 2008, Journal of chemical information and modeling,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Docking-based 3D-QSAR analyses of pyrazole derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.
April 2012, Journal of molecular modeling,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors: A Combinatorial Approach.
December 2017, Biochemistry. Biokhimiia,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Docking-based 3D-QSAR and pharmacophore studies on diarylpyrimidines as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
February 2019, Molecular diversity,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
NMR characterization of HIV-1 reverse transcriptase binding to various non-nucleoside reverse transcriptase inhibitors with different activities.
October 2015, Scientific reports,
R Gussio, and N Pattabiraman, and D W Zaharevitz, and G E Kellogg, and I A Topol, and W G Rice, and C A Schaeffer, and J W Erickson, and S K Burt
Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors.
February 2006, Current opinion in investigational drugs (London, England : 2000),
Copied contents to your clipboard!