caa a22 4500 605511314 CHVBK 20210128100650.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00894-015-2774-2 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2774-2 Computational design, functional analysis and antigenic epitope estimation of a novel hybrid of 12 peptides of hirudin and reteplase [Elektronische Daten] [Yingting Cai, Jingxiao Bao, Xingzhen Lao, Heng Zheng, Jianhua Chen, Rong Yu] Cardiovascular and cerebrovascular diseases are leading causes of morbidity and mortality for human beings, and thrombosis is the major risk factor. Thrombolytic therapy has been testified to be the most effective approach to cure thrombosis-related diseases. In clinical treatment, we often adopt a combination therapeutic regimen of both thrombolytic and anticoagulant agents to prevent the recurrence of thrombosis. Thus, a novel hybrid (HV12p-rPA) comprised of the C-terminal 12 residues of hirudin-PA (HV12p) and reteplase (rPA) was designed. The three-dimensional structure of this hybrid was mimicked based on homology modeling and refined with dynamics simulation by utilizing Amber12.0 software. The function of the hybrid was analyzed by structure comparison and the root mean square deviation (RMSD) of Cα atoms between the hybrid and native rPA was calculated. The results showed that HV12p, which was located in the N-terminus of the hybrid, was far from the rPA segment of the hybrid and had no influence on the conformational stability of the rPA domain. The RMSD of Cα atoms of these superimposed proteins was about 40Å, implying that the hybrid had a similar spatial conformation to that of native rPA. Additionally, the antigenic epitopes of the hybrid were predicted by estimations of Hopp-Wood hydrophilicity, Janin accessibility, Zimmermane-Simha polarity, Bhaskaran-Ponnuswamy flexibility, as well as secondary structure analysis and Kolaskar-Tongaonkar antigenicity prediction. The results showed that the most likely antigenic determinants were located at or near regions 148-152, 257-262 and 321-330. Springer-Verlag Berlin Heidelberg, 2015 C-terminal 12 residue of hirudin-PA nationallicence Reteplase nationallicence Three-dimensional structure prediction nationallicence Function analysis nationallicence Antigenic epitope estimation nationallicence Cai Yingting Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, 610041, Chengdu, China aut Bao Jingxiao China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut Lao Xingzhen China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut Zheng Heng China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut Chen Jianhua China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut Yu Rong Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, 610041, Chengdu, China aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-9 1610-2940 21:9<1 2015 21 894 https://doi.org/10.1007/s00894-015-2774-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2774-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cai Yingting Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, 610041, Chengdu, China aut NATIONALLICENCE 700 1- Bao Jingxiao China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut NATIONALLICENCE 700 1- Lao Xingzhen China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut NATIONALLICENCE 700 1- Zheng Heng China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut NATIONALLICENCE 700 1- Chen Jianhua China Pharmaceutical University, No.24, Tongjiaxiang, 210009, Nanjing, China aut NATIONALLICENCE 700 1- Yu Rong Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, 610041, Chengdu, China aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-9 1610-2940 21:9<1 2015 21 894