TY - JOUR
T1 - Exploring the potential binding sites of some known HDAC inhibitors on some HDAC8 conformers by docking studies
AU - Sixto-López, Yudibeth
AU - Gómez-Vidal, José A.
AU - Correa-Basurto, José
N1 - Funding Information:
Acknowledgments The work was supported by grants from CONACYT (132353), CYTED: 214RT0482, PIFI-SIP-COFAA, grant SIP20140252, from IPN, and scholarships to YSL from CONACYT. Finally, we thank to the referee for their fruitful suggestions.
PY - 2014/8
Y1 - 2014/8
N2 - We describe the conformational behavior of histone deacetylase 8 (HDAC8) using molecular dynamics (MD) simulations. HDAC8 conformers were used for the docking studies using some known HDAC inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), aroyl-pyrrole-hydroxy-amide (APHA-8) and tubacin to explore their interactions, binding modes, free energy values. The MD simulation show that HDAC8 make important surface changes at the catalytic site (CS) entrance as well as at two entrances locations in the 14-Å tunnel. In addition, we identify an alternate entrance to the 14-Å tunnel named adjacent to the catalytic site pocket (ACSP). By using docking studies, it was possible to elucidate the importance of hydrophobic and π-π interactions that are the most important for the ligand-HDAC8 complex structural stabilization. In conclusion, the ligand flexibility, molecular weight and chemical moieties (hydroxamic acid, aryl and aliphatic moieties) are the principal properties required to increase the binding affinity on HDAC8.
AB - We describe the conformational behavior of histone deacetylase 8 (HDAC8) using molecular dynamics (MD) simulations. HDAC8 conformers were used for the docking studies using some known HDAC inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), aroyl-pyrrole-hydroxy-amide (APHA-8) and tubacin to explore their interactions, binding modes, free energy values. The MD simulation show that HDAC8 make important surface changes at the catalytic site (CS) entrance as well as at two entrances locations in the 14-Å tunnel. In addition, we identify an alternate entrance to the 14-Å tunnel named adjacent to the catalytic site pocket (ACSP). By using docking studies, it was possible to elucidate the importance of hydrophobic and π-π interactions that are the most important for the ligand-HDAC8 complex structural stabilization. In conclusion, the ligand flexibility, molecular weight and chemical moieties (hydroxamic acid, aryl and aliphatic moieties) are the principal properties required to increase the binding affinity on HDAC8.
KW - APHA
KW - Docking
KW - HDAC8
KW - Molecular dynamic simulations
KW - SAHA
KW - Tubacin
KW - VPA
UR - http://www.scopus.com/inward/record.url?scp=84906059833&partnerID=8YFLogxK
U2 - 10.1007/s12010-014-0976-1
DO - 10.1007/s12010-014-0976-1
M3 - Artículo
C2 - 24888409
SN - 0273-2289
VL - 173
SP - 1907
EP - 1926
JO - Applied Biochemistry and Biotechnology
JF - Applied Biochemistry and Biotechnology
IS - 7
ER -