TY - JOUR
T1 - The electronic structure of human erythropoietin as an aid in the design of oxidation-resistant therapeutic proteins
AU - Pichierri, Fabio
N1 - Funding Information:
I thank Fujitsu Ltd. (Tokyo) for providing the MOPAC2002 software package and the XMO graphical user interface. Two anonymous referees are gratefully acknowledged for useful comments and constructive criticisms. Financial support for this work was provided by the 21st century Center of Excellence (COE) project ‘Giant Molecules and Complex Systems’ of MEXT activated at Tohoku University.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - The electronic structure of human erythropoietin (HuEPO) has been investigated with the aid of quantum mechanical calculations. The results indicate that the protein is highly polarized and its permanent dipole moment has a magnitude of 471 D. The HOMO of HuEPO is localized on Trp51, which stays in close proximity to Met54. Three oxidation-resistant mutants of HuEPO (W51F, M54V, and W51F-M54V) have been modeled and their electronic structures are compared to that of the native protein. Among them, the W51F mutation is predicted to be the most effective in increasing the oxidation potential of the protein.
AB - The electronic structure of human erythropoietin (HuEPO) has been investigated with the aid of quantum mechanical calculations. The results indicate that the protein is highly polarized and its permanent dipole moment has a magnitude of 471 D. The HOMO of HuEPO is localized on Trp51, which stays in close proximity to Met54. Three oxidation-resistant mutants of HuEPO (W51F, M54V, and W51F-M54V) have been modeled and their electronic structures are compared to that of the native protein. Among them, the W51F mutation is predicted to be the most effective in increasing the oxidation potential of the protein.
KW - Anemia
KW - Computational chemistry
KW - Erythropoietin
KW - Protein-based therapeutics
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U2 - 10.1016/j.bmcl.2005.10.041
DO - 10.1016/j.bmcl.2005.10.041
M3 - Article
C2 - 16289823
AN - SCOPUS:29544452805
VL - 16
SP - 587
EP - 591
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -