含9肽HLA-A0201分子结构数据的分析

目的：了解HLA-A*0201分子结构数据中蕴藏的信息,为抗原肽与HLA-A*0201分子对接(Docking)提供约束规则和选择对接后备选抗原肽提供参考。方法：从蛋白质结构数据库PDB中下载所有HLA-A分子的数据,然后利用数据库VFP编程来进行对HLA-A分子结构数据筛选,对所得的HLA-A*0201分

http://doc.guandang.netData analysis of HLA-A*0201 bound peptide nonamers in PDBZHANG Ru-xiang, HUANG Qing-hai, ZHANG Jian-qiong, XIE Wei* Genetics Research Center, Southeast University Medical School, Nanjing 210009, ChinaKey words human leucocyte antigen; peptide nonamers; structural data; molecular dockingFirst author ZHANG Ru-xiang E-mail: zrxyxxm@http://doc.guandang.netCorresponding author Dr XIE Wei Department of Genetics and Developmental Biology Dingjiaqiao 87, Nanjing Jiangsu province, P. R. China Tel:86 25 83272510 Fax:86 25 83272510 E-mail:Wei.xie@http://doc.guandang.netAbstract HLA structural data were downloaded from PDB. All data were filtered by programming and were managed in the Visual FoxPro (VFP). With Biopolymer module of InsigtII software, hydrogen atoms were added to filtered molecules. Then, the program was utilized to analyze distances of every two Cα atoms of peptide nonamers and amino acid residues of HLA involved within a different distance around 26 peptide nonamers respectively. There were 26 HLA-A*0201 complexes with peptide nonamers in PDB. The position 2(P2) of 21 peptides was Leu. Meanwhile, P9 was either Leu or Val mostly (25/26). The mean number of H-bond between P1 and molecule HLA-A*0201 was 1.86, while those at P2 and P9 were 1.81, 1.95 respectively. By method of moment, some distances of two C α atoms appeared normal school. Some amino acid residues of HLA, such as Tyr7, Glu63, Lys66, His70, Thr73, Ser77, Leu81, Tyr99, Thr143, Trp147 and Tyr171, appeared above 90% within a distance of 0.25 nm around peptide nonamers. P1 maybe is anchoring residue, just like P2 and P9. Distances of two Cα atoms of peptide nonamers can be utilized to check whether the structure of peptide is reasonable after molecular docking. Some high frequency residues can be applied to adjust binding subset for dockingThe HLA (human leucocyte antigen) is highly polymorphic in individuals. The HLA gene is located on the short arm of chromosome 6, which encodes two distinct classes of cell surface molecules, I and II. Class I molecules are expressed on the surfaces of virtually all nucleated cells at varying densities, while class II molecules are more restricted to cells of the immune system, primarily B lymphocytes and monocytes. The proof implies that the reason tumor cell can be cloning and has metastasis behavior, is not so much that body’s immune system exists defection, but itself has ability to escape the supervision of immune system. The further studies certify that peptide–HLA complexes are extremely stable under physiological conditions and, given this high affinity, only a small fraction of the class I molecules are normally found on the cell surface without bound peptide, only the high affinity of antigen peptide binding HLA couldn’t be degraded by endoplasmic reticulum. Cellular immunity plays an important role in antitumor, especially main effector cell-CTL. Many works involving in peptide vaccine have been launched, which can activate antitumor cytotoxic T cells (1~7). Peptide vaccine can make tumor diminution; even complete extinction (5).1

目的：了解HLA-A*0201分子结构数据中蕴藏的信息,为抗原肽与HLA-A*0201分子对接(Docking)提供约束规则和选择对接后备选抗原肽提供参考。方法：从蛋白质结构数据库PDB中下载所有HLA-A分子的数据,然后利用数据库VFP编程来进行对HLA-A分子结构数据筛选,对所得的HLA-A*0201分

http://doc.guandang.netOne of the methods to design peptide vaccine is to modify epitopes, but the premise of modifying amino acid residues is to increase the affinity between HLA and peptide. Usually, the T2 cell line is used to detect their affinity by fluorescent index (7). With the development of molecular mechanics and computer, and the application of molecular docking in the biological field, it is possible to use software to dock small molecule to big molecule. In this study, we wanted to investigate structural information hiding in data of peptide-HLA complexes in order to offer rules for molecular docking and select a reasonable structure of peptide nonamers docked with HLA-A*0201. HLA structural data were downloaded from the Protein Data Bank (PDB) (8). All data were filtered by programming and were managed in the Visual FoxPro (VFP). With Biopolymer module of InsigtII software, hydrogen atoms were added to filtered data. Distances of two Cα atoms could be calculated by following formula. Method of moment was used to judge whether distances of two Cα atoms appear normal school（α=0.05）. Using above formula, amino acids of HLA involved within a distance of 2.5 angstrom to 4 angstrom around peptide nonamers respectively.Di,i+1=√(xi-xi+1)2+(yi-yi+1)2+(zi-zi+1)2(1≤i≤8)There were 26 HLA-A*0201 complexes with peptide nonamers in PDB. Fifteen of 26 HLA-A*0201 complexes were dimer; one was quartomer. The position 2(P2) of 21 peptides was Leu. Meanwhile, P9 was either Leu or Val mostly (Tab1). By method of moment, some distances of two Cα atoms appeared normal school(Tab2). Some amino acid residues of HLA, such as Tyr7, Glu63, Lys66, His70, Thr73, Ser77, Leu81, Tyr99, Thr143, Trp147 and Tyr171, appeared above 90% within a distance of 2.5 angstrom around peptide nonamers (Tab3). P1 was as close to HLA as P2 and P9 were (Fig1,2). The total number of H-bond between all P1 and molecule HLA-A2 was 82, while those at P2 and P9 were 80,86 respectively. Tab 1 Twenty-six sequences of peptide nonamers binding HLA-A*0201 respectivelyID 1AKJ 1HHJ 1P7Q 1AO7 1BD2 1DUZ 1HHK 1IM3 1QRN 1QSE 1QSF 1B0G 1LP9 LLFGYAVYV LLFGYPRYV LLFGYPVAV ALWGFFPVL LLFGYPVYV ILKEPVHGV aa sequence ID 1I7T 1I7U 1HHI 1OGA 1EEY 1HHG 1I1F 1I1Y 1I7R 1JHT 1Q94 1QEW 1QR1 aa sequence ALWGVFPVL ALWGFVPVL GILGFVFTL ILSALVGIV TLTSCNTS …… 此处隐藏：12801字，全部文档内容请下载后查看。喜欢就下载吧 ……