基于蛋白复合物PDB设计干扰多态之三（LoopFinder）

       在文章Comprehensive analysis of loops at protein-protein interfaces for macrocycle design中介绍了LoopFinder及其所找到的对于蛋白结合较为关键的loop区域。此文的基本内容框架如附图1所示：

      其中对于loop的具体判断依据为Interface residues were identified as any amino acid containing at least one heavy atom within 6.5 Å of another heavy atom on the partner chain. Loops were then identified using the following criteria: (i) loops contain 4–8 consecutive amino acids, a length suitable for incorporation into a synthetically feasible cyclic peptide; (ii) the Cα-Cα distance of the loop termini is limited to a maximum of 6.2 Å for loops of 6–8 amino acids (4.67 Å for 4-amino-acid loops; 5.83 Å for 5-amino-acid loops) to exclude extended secondary structure elements such as α-helices and β-strands and to ensure that the N and C termini of the loop are in relative positions amenable to cyclization; (iii) loops must contain at least 80% interface residues (at least one heavy atom within 6.5 Å of another heavy atom on the partner chain).

hot loop的判断依据为To generate the set of hot loops, we identified loops with two consecutive hot spots, loops with at least three hot spots and loops for which the average ΔΔGresidue was greater than 1 kcal mol−1.

能量的计算方法Interface loops were then subjected to a computational alanine scan using PyRosetta v2.012 and Rosetta 3.0. The PyRosetta alanine scanning script originally developed by the Gray lab (http://graylab.jhu.edu/pyrosetta/downloads/pyrosetta_scripts/ala_scan.zip) was modified to implement a modified score function and to be run in a parallel manner on Tufts’ research cluster.

loop的计算此研究团队提供了webserver：Loop Finder Submission Form (tufts.edu)，且发表了另一篇研究文章Analysis of Loops that Mediate Protein-Protein Interactions and Translation into Sub-Micromolar Inhibitors，一些loop区域在文章附近中可以查到。