Abstract

The construction of three-dimensional models of protein macromolecules is a serious challenge due to the possible ambiguity of solving the inverse problem of reconstructing a three-dimensional structure from a one-dimensional small-angle scattering profile. The target function of this task can have several local minima, which leads to the dependence of the solution on the initial values of the model parameters and on the method of finding the global minimum. The problem of creating structural models is also complicated by averaging the scattering pattern over all orientations of particles in space and by the size and shape distribution of scattering objects in the case of polydispersity and/or polymorphism. In this study, the issue of ambiguity in solving inverse problems and restoring the three-dimensional structure of a protein is considered using the structure of the ectodomain of an insulin receptor-related receptor (ectoIRR) in solution as an example. The paper presents a consistent approach to solving this problem, starting from the determination of general structural parameters and ab initio reconstruction of shape to modeling by rigid bodies (using molecular tectonics), hybrid methods, and analysis of scattering profiles by singular vector decomposition.

中文翻译：

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解决小角度散射反问题的歧义问题：以胰岛素受体相关受体为例的一致方法。解释 SAXS 数据的方法

摘要

蛋白质大分子三维模型的构建是一个严峻的挑战，因为解决从一维小角度散射剖面重建三维结构的逆问题可能存在歧义。这个任务的目标函数可以有几个局部最小值，这导致解依赖于模型参数的初始值和寻找全局最小值的方法。由于在空间中粒子的所有方向上平均散射模式以及在多分散性和/或多态性的情况下散射对象的大小和形状分布，创建结构模型的问题也变得复杂。在这项研究中，以解决方案中胰岛素受体相关受体（ectoIRR）胞外域的结构为例，考虑求解逆问题和恢复蛋白质三维结构中的歧义问题。本文提出了解决这个问题的一致方法，从确定一般结构参数和通过刚体（使用分子构造）、混合方法和通过奇异向量分解分析散射轮廓，从头开始重建形状以进行建模。