TY - JOUR
T1 - Structural studies of human purine nucleoside phosphorylase
T2 - Towards a new specific empirical scoring function
AU - Timmers, Luis Fernando Saraiva Macedo
AU - Caceres, Rafael Andrade
AU - Vivan, Ana Luiza
AU - Gava, Lisandra Marques
AU - Dias, Raquel
AU - Ducati, Rodrigo Gay
AU - Basso, Luiz Augusto
AU - Santos, Diogenes Santiago
AU - de Azevedo, Walter Filgueira
N1 - Funding Information:
This work was supported by grants from CNPq, CAPES and Instituto do Milênio (CNPq-MCT). W.F.A., D.S.S., and L.A.B. are senior researchers of CNPq (Conselho Nacional de Pesquisas, Brazil).
PY - 2008/11/1
Y1 - 2008/11/1
N2 - Human purine nucleoside phosphorylase (HsPNP) is a target for inhibitor development aiming at T-cell immune response modulation. In this work, we report the development of a new set of empirical scoring functions and its application to evaluate binding affinities and docking results. To test these new functions, we solved the structure of HsPNP and 2-mercapto-4(3H)-quinazolinone (HsPNP:MQU) binary complex at 2.7 Å resolution using synchrotron radiation, and used these functions to predict ligand position obtained in docking simulations. We also employed molecular dynamics simulations to analyze HsPNP in two conditions, as apoenzyme and in the binary complex form, in order to assess the structural features responsible for stability. Analysis of the structural differences between systems provides explanation for inhibitor binding. The use of these scoring functions to evaluate binding affinities and molecular docking results may be used to guide future efforts on virtual screening focused on HsPNP.
AB - Human purine nucleoside phosphorylase (HsPNP) is a target for inhibitor development aiming at T-cell immune response modulation. In this work, we report the development of a new set of empirical scoring functions and its application to evaluate binding affinities and docking results. To test these new functions, we solved the structure of HsPNP and 2-mercapto-4(3H)-quinazolinone (HsPNP:MQU) binary complex at 2.7 Å resolution using synchrotron radiation, and used these functions to predict ligand position obtained in docking simulations. We also employed molecular dynamics simulations to analyze HsPNP in two conditions, as apoenzyme and in the binary complex form, in order to assess the structural features responsible for stability. Analysis of the structural differences between systems provides explanation for inhibitor binding. The use of these scoring functions to evaluate binding affinities and molecular docking results may be used to guide future efforts on virtual screening focused on HsPNP.
KW - Docking
KW - Empirical scoring functions
KW - Enzymology
KW - Molecular dynamics
KW - Quinazolinone
KW - Virtual screening
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U2 - 10.1016/j.abb.2008.08.015
DO - 10.1016/j.abb.2008.08.015
M3 - Article
C2 - 18790691
AN - SCOPUS:53649090302
SN - 0003-9861
VL - 479
SP - 28
EP - 38
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -