虚拟筛选原理及应用示例.pptVIP

2. DOCK4.0 2.1 Workflow of Dock4.01 DOCK4.0 优点： 计算速度较快； 使用广泛； 用于蛋白质-配体及蛋白质-蛋白质对接； 基于立场的打分函数更加倾向于形状匹配； 适合活性位点为非极性口袋。 DOCK4.0 缺点： 不适合极性口袋； 使用单纯型优化方法,初始位置至关重要； 结果较大程度依赖于球集； 无法作自由能预测； 没考虑溶剂化效应。 Chemical score 不准确。 Generate the site surface. There are 5 files in the 1_str 6cox.pdb 6cox_com.pdb exclude.pdb 6cox.mol2 6cox_lig.mol2 autoMS 6cox.pdb sphgen ls mv 6cox.sph INSPH OUTSPH ../2* cd ../2* showsphere Enter name of sphere cluster file: 6cox.sph Enter cluster number to process (0 = all): 1 Generate surfaces as well as pdb files (N/Y)? n Enter name for output PDB file name: sph.pdb 2.3 DOCK4.0操作步骤及实例 Display the 6cox.ms using UCSF Chimera This creates INSPH and 6cox.ms files. DOCK 3.5 receptor_spheres cluster 1 number of spheres in cluster 34 You can modify the sphere(add or delete). Also, you can modify the INSPH Display the sphere. 2.3 DOCK4.0操作步骤及实例 Generate the box 2.3 DOCK4.0操作步骤及实例 showbox automatically construct box to enclose spheres [Y/N]?y extra margin to also be enclosed (angstroms)? (this will be added in all 6 directions) 3.5 sphere file- 6cox.sph cluster number- 1 output filename? box.pdb finished making pdb-format box file Scoring Grid Calculation grid4 –i grid.in 2.3 DOCK4.0操作步骤及实例 compute_grids yes grid_spacing 0.3 output_molecule no contact_score no chemical_score no energy_score yes energy_cutoff_distance 10 atom_model a attractive_exponent 6 repulsive_exponent 12 distance_dielectric yes dielectric_factor 4 bump_filter yes bump_overlap 0.75 receptor_file ../1_str/6cox.mol2 box_file ../2_site/box.pdb vdw_definition_file /disk2/program/dock4/parameter/vdw.defn score_grid_prefix 6cox This will create 3 files: grid.in 6cox.nrg 6cox.bmp