Identification of Binding Mode and Prospective Structural Features of Novel Nef Protein Inhibitors as Potential Anti-HIV Drugs.
Identifieur interne : 003B98 ( Ncbi/Checkpoint ); précédent : 003B97; suivant : 003B99Identification of Binding Mode and Prospective Structural Features of Novel Nef Protein Inhibitors as Potential Anti-HIV Drugs.
Auteurs : Suri Moonsamy [Afrique du Sud] ; Soumendranath Bhakat [Afrique du Sud] ; Muthusamy Ramesh [Afrique du Sud] ; Mahmoud E S. Soliman [Afrique du Sud]Source :
- Cell biochemistry and biophysics [ 1559-0283 ] ; 2017.
Descripteurs français
- KwdFr :
- Agents antiVIH (), Bibliothèques de petites molécules, Domaines protéiques, Humains, Interactions hydrophobes et hydrophiles, Liaison aux protéines, Liaison hydrogène, Ligands, Produits du gène nef du virus de l'immunodéficience humaine (), Produits du gène nef du virus de l'immunodéficience humaine (antagonistes et inhibiteurs), Relation structure-activité, Simulation de docking moléculaire, Simulation de dynamique moléculaire, Thermodynamique, Évaluation préclinique de médicament.
- MESH :
- antagonistes et inhibiteurs : Produits du gène nef du virus de l'immunodéficience humaine.
- Agents antiVIH, Bibliothèques de petites molécules, Domaines protéiques, Humains, Interactions hydrophobes et hydrophiles, Liaison aux protéines, Liaison hydrogène, Ligands, Produits du gène nef du virus de l'immunodéficience humaine, Relation structure-activité, Simulation de docking moléculaire, Simulation de dynamique moléculaire, Thermodynamique, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Anti-HIV Agents (chemistry), Drug Evaluation, Preclinical, Humans, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Ligands, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, Protein Domains, Small Molecule Libraries, Structure-Activity Relationship, Thermodynamics, nef Gene Products, Human Immunodeficiency Virus (antagonists & inhibitors), nef Gene Products, Human Immunodeficiency Virus (chemistry).
- MESH :
- chemical , antagonists & inhibitors : nef Gene Products, Human Immunodeficiency Virus.
- chemical , chemistry : Anti-HIV Agents, nef Gene Products, Human Immunodeficiency Virus.
- Drug Evaluation, Preclinical, Humans, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Ligands, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, Protein Domains, Small Molecule Libraries, Structure-Activity Relationship, Thermodynamics.
Abstract
Human immunodeficiency virus (HIV)-negative factor (Nef) protein is an accessory pathogenic factor, which plays a significant role in acquired immune deficiency syndrome (AIDS). Nef deficient HIV virus took a longer time to progress into AIDS. Therefore, targeting Nef protein is considered as a key strategy towards HIV/AIDS treatment. Up-to-date, only few compounds were reported as Nef inhibitors. This has prompted us to provide a first account of an integrated computational framework in order to identify more potential Nef inhibitors. Herein, using a hybrid ligand (shape similarity and pharmacophore) and structure-(molecular docking) based virtual screening approaches combined with molecular dynamics as well as post dynamics analysis, potential new hits were identified as HIV-Nef inhibitors. The top ranked compounds of molecular docking from the shape similarity-based library (ZINC04177596, ∆ G bind= -28.7482 kcal/mol) and pharmacophore-based library (ZINC36617540, ∆ G bind= -20.2271 kcal/mol) possess comparatively better binding affinities than the reference molecule, B9 (∆ G bind = -18.0694 kcal/mol). Both these hits (ZINC04177596 and ZINC36617540) showed similar binding mode at the binding site as like the prototype, B9. Hydrophobic and electrostatic interactions seemed to be the prominent binding forces that hold these ligands at the dimer interface of Nef protein. Finally, a set of chemical structural features that can be used as a guide in the design of novel potential Nef inhibitors is also highlighted herein. We believe that the information gained from this study would be of great importance in the discovery and design of potential small molecules targeting HIV-Nef.
DOI: 10.1007/s12013-016-0774-1
PubMed: 27981421
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000824
- to stream PubMed, to step Curation: 000824
- to stream PubMed, to step Checkpoint: 000824
- to stream Ncbi, to step Merge: 003B98
- to stream Ncbi, to step Curation: 003B98
Links to Exploration step
pubmed:27981421Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of Binding Mode and Prospective Structural Features of Novel Nef Protein Inhibitors as Potential Anti-HIV Drugs.</title><author><name sortKey="Moonsamy, Suri" sort="Moonsamy, Suri" uniqKey="Moonsamy S" first="Suri" last="Moonsamy">Suri Moonsamy</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Bhakat, Soumendranath" sort="Bhakat, Soumendranath" uniqKey="Bhakat S" first="Soumendranath" last="Bhakat">Soumendranath Bhakat</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Ramesh, Muthusamy" sort="Ramesh, Muthusamy" uniqKey="Ramesh M" first="Muthusamy" last="Ramesh">Muthusamy Ramesh</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Soliman, Mahmoud E S" sort="Soliman, Mahmoud E S" uniqKey="Soliman M" first="Mahmoud E S" last="Soliman">Mahmoud E S. Soliman</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa. soliman@ukzn.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27981421</idno><idno type="pmid">27981421</idno><idno type="doi">10.1007/s12013-016-0774-1</idno><idno type="wicri:Area/PubMed/Corpus">000824</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000824</idno><idno type="wicri:Area/PubMed/Curation">000824</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000824</idno><idno type="wicri:Area/PubMed/Checkpoint">000824</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000824</idno><idno type="wicri:Area/Ncbi/Merge">003B98</idno><idno type="wicri:Area/Ncbi/Curation">003B98</idno><idno type="wicri:Area/Ncbi/Checkpoint">003B98</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of Binding Mode and Prospective Structural Features of Novel Nef Protein Inhibitors as Potential Anti-HIV Drugs.</title><author><name sortKey="Moonsamy, Suri" sort="Moonsamy, Suri" uniqKey="Moonsamy S" first="Suri" last="Moonsamy">Suri Moonsamy</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Bhakat, Soumendranath" sort="Bhakat, Soumendranath" uniqKey="Bhakat S" first="Soumendranath" last="Bhakat">Soumendranath Bhakat</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Ramesh, Muthusamy" sort="Ramesh, Muthusamy" uniqKey="Ramesh M" first="Muthusamy" last="Ramesh">Muthusamy Ramesh</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author><author><name sortKey="Soliman, Mahmoud E S" sort="Soliman, Mahmoud E S" uniqKey="Soliman M" first="Mahmoud E S" last="Soliman">Mahmoud E S. Soliman</name><affiliation wicri:level="1"><nlm:affiliation>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa. soliman@ukzn.ac.za.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001</wicri:regionArea><wicri:noRegion>4001</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell biochemistry and biophysics</title><idno type="eISSN">1559-0283</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-HIV Agents (chemistry)</term><term>Drug Evaluation, Preclinical</term><term>Humans</term><term>Hydrogen Bonding</term><term>Hydrophobic and Hydrophilic Interactions</term><term>Ligands</term><term>Molecular Docking Simulation</term><term>Molecular Dynamics Simulation</term><term>Protein Binding</term><term>Protein Domains</term><term>Small Molecule Libraries</term><term>Structure-Activity Relationship</term><term>Thermodynamics</term><term>nef Gene Products, Human Immunodeficiency Virus (antagonists & inhibitors)</term><term>nef Gene Products, Human Immunodeficiency Virus (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agents antiVIH ()</term><term>Bibliothèques de petites molécules</term><term>Domaines protéiques</term><term>Humains</term><term>Interactions hydrophobes et hydrophiles</term><term>Liaison aux protéines</term><term>Liaison hydrogène</term><term>Ligands</term><term>Produits du gène nef du virus de l'immunodéficience humaine ()</term><term>Produits du gène nef du virus de l'immunodéficience humaine (antagonistes et inhibiteurs)</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Simulation de dynamique moléculaire</term><term>Thermodynamique</term><term>Évaluation préclinique de médicament</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>nef Gene Products, Human Immunodeficiency Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-HIV Agents</term><term>nef Gene Products, Human Immunodeficiency Virus</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Produits du gène nef du virus de l'immunodéficience humaine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Drug Evaluation, Preclinical</term><term>Humans</term><term>Hydrogen Bonding</term><term>Hydrophobic and Hydrophilic Interactions</term><term>Ligands</term><term>Molecular Docking Simulation</term><term>Molecular Dynamics Simulation</term><term>Protein Binding</term><term>Protein Domains</term><term>Small Molecule Libraries</term><term>Structure-Activity Relationship</term><term>Thermodynamics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Agents antiVIH</term><term>Bibliothèques de petites molécules</term><term>Domaines protéiques</term><term>Humains</term><term>Interactions hydrophobes et hydrophiles</term><term>Liaison aux protéines</term><term>Liaison hydrogène</term><term>Ligands</term><term>Produits du gène nef du virus de l'immunodéficience humaine</term><term>Relation structure-activité</term><term>Simulation de docking moléculaire</term><term>Simulation de dynamique moléculaire</term><term>Thermodynamique</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human immunodeficiency virus (HIV)-negative factor (Nef) protein is an accessory pathogenic factor, which plays a significant role in acquired immune deficiency syndrome (AIDS). Nef deficient HIV virus took a longer time to progress into AIDS. Therefore, targeting Nef protein is considered as a key strategy towards HIV/AIDS treatment. Up-to-date, only few compounds were reported as Nef inhibitors. This has prompted us to provide a first account of an integrated computational framework in order to identify more potential Nef inhibitors. Herein, using a hybrid ligand (shape similarity and pharmacophore) and structure-(molecular docking) based virtual screening approaches combined with molecular dynamics as well as post dynamics analysis, potential new hits were identified as HIV-Nef inhibitors. The top ranked compounds of molecular docking from the shape similarity-based library (ZINC04177596, ∆ G bind= -28.7482 kcal/mol) and pharmacophore-based library (ZINC36617540, ∆ G bind= -20.2271 kcal/mol) possess comparatively better binding affinities than the reference molecule, B9 (∆ G bind = -18.0694 kcal/mol). Both these hits (ZINC04177596 and ZINC36617540) showed similar binding mode at the binding site as like the prototype, B9. Hydrophobic and electrostatic interactions seemed to be the prominent binding forces that hold these ligands at the dimer interface of Nef protein. Finally, a set of chemical structural features that can be used as a guide in the design of novel potential Nef inhibitors is also highlighted herein. We believe that the information gained from this study would be of great importance in the discovery and design of potential small molecules targeting HIV-Nef.</div></front></TEI><affiliations><list><country><li>Afrique du Sud</li></country></list><tree><country name="Afrique du Sud"><noRegion><name sortKey="Moonsamy, Suri" sort="Moonsamy, Suri" uniqKey="Moonsamy S" first="Suri" last="Moonsamy">Suri Moonsamy</name></noRegion><name sortKey="Bhakat, Soumendranath" sort="Bhakat, Soumendranath" uniqKey="Bhakat S" first="Soumendranath" last="Bhakat">Soumendranath Bhakat</name><name sortKey="Ramesh, Muthusamy" sort="Ramesh, Muthusamy" uniqKey="Ramesh M" first="Muthusamy" last="Ramesh">Muthusamy Ramesh</name><name sortKey="Soliman, Mahmoud E S" sort="Soliman, Mahmoud E S" uniqKey="Soliman M" first="Mahmoud E S" last="Soliman">Mahmoud E S. Soliman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/SidaSubSaharaV1/Data/Ncbi/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003B98 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd -nk 003B98 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= SidaSubSaharaV1
|flux= Ncbi
|étape= Checkpoint
|type= RBID
|clé= pubmed:27981421
|texte= Identification of Binding Mode and Prospective Structural Features of Novel Nef Protein Inhibitors as Potential Anti-HIV Drugs.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Checkpoint/RBID.i -Sk "pubmed:27981421" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a SidaSubSaharaV1
| This area was generated with Dilib version V0.6.32. |  |