Understanding PIM-1 kinase inhibitor interactions with free energy simulation

2019 ◽  
Vol 21 (14) ◽  
pp. 7544-7558 ◽  
Author(s):  
Xiaohui Wang ◽  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Kinase Inhibitor ◽  
Integration Site ◽  
Leukemia Virus ◽  
Energy Simulation ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Moloney Leukemia Virus

The proviral integration site of the Moloney leukemia virus (PIM) family includes three homologous members.

scholarly journals Identification of a novel common proviral integration site, flit-1, in feline leukemia virus induced thymic lymphoma

Virology ◽  
2009 ◽  
Vol 386 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Yasuhito Fujino ◽  
Chun-Peng Liao ◽  
Yan Shi Zhao ◽  
Judong Pan ◽  
Lawrence E. Mathes ◽  
...  
Keyword(s):  
Integration Site ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Proviral Integration ◽  
Thymic Lymphoma ◽  
Proviral Integration Site

scholarly journals Proviral Integration Site for Moloney Murine Leukemia Virus (PIM) Kinases Promote Human T Helper 1 Cell Differentiation

2012 ◽  
Vol 288 (5) ◽  
pp. 3048-3058 ◽  
Author(s):  
Johanna Tahvanainen ◽  
Minna K. Kyläniemi ◽  
Kartiek Kanduri ◽  
Bhawna Gupta ◽  
Hanna Lähteenmäki ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
T Helper ◽  
T Helper 1 ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Pim Kinases ◽  
Murine Leukemia

scholarly journals Fre2, a proviral integration site of Friend murine leukemia virus that is closely linked to Fv2

Leukemia ◽  
1997 ◽  
Vol 11 (5) ◽  
pp. 619-623 ◽  
Author(s):  
RW Friedrich ◽  
M Veit ◽  
D Eisel ◽  
U Friedrich ◽  
M Pass ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Murine Leukemia

scholarly journals Insights into the Interaction Mechanisms of the Proviral Integration Site of Moloney Murine Leukemia Virus (Pim) Kinases with Pan-Pim Inhibitors PIM447 and AZD1208: A Molecular Dynamics Simulation and MM/GBSA Calculation Study

2019 ◽  
Vol 20 (21) ◽  
pp. 5410 ◽  
Author(s):  
Qingqing Chen ◽  
Yan Wang ◽  
Shanshan Shi ◽  
Kaihang Li ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Proviral Integration ◽  
Interaction Mechanisms ◽  
Proviral Integration Site ◽  
Pim Kinases ◽  
Murine Leukemia

Based on the up-regulation of the proviral integration site of the Moloney murine leukemia virus (Pim) kinase family (Pim1, 2, and 3) observed in several types of leukemias and lymphomas, the development of pan-Pim inhibitors is an attractive therapeutic strategy. While only PIM447 and AZD1208 have entered the clinical stages. To elucidate the interaction mechanisms of three Pim kinases with PIM447 and AZD1208, six Pim/ligand systems were studied by homology modeling, molecular docking, molecular dynamics (MD) simulation and molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy calculation. The residues of the top group (Leu44, Val52, Ala65, Lys67, and Leu120 in Pim1) dominated the pan-Pim inhibitors binding to Pim kinases. The residues of the bottom group (Gln127, Asp128, and Leu174 in Pim1) were crucial for Pims/PIM447 systems, while the contributions of these residues were decreased sharply for Pims/AZD1208 systems. It is likely that the more potent pan-Pim inhibitors should be bound strongly to the top and bottom groups. The residues of the left, right and loop groups were located in the loop regions of the binding pocket, however, the flexibility of these regions triggered the protein interacting with diverse pan-Pim inhibitors efficiently. We hope this work can provide valuable information for the design of novel pan-Pim inhibitors in the future.

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