Universität Hamburg, ZBH - Center for Bioinformatics, Bundesstraße 43, 20146 Hamburg, Germany.
J Chem Inf Model. 2023 Apr 24;63(8):2573-2585. doi: 10.1021/acs.jcim.3c00100. Epub 2023 Apr 5.
In many molecular modeling applications, the standard procedure is still to handle proteins as single, rigid structures. While the importance of conformational flexibility is widely known, handling it remains challenging. Even the crystal structure of a protein usually contains variability exemplified in alternate side chain orientations or backbone segments. This conformational variability is encoded in PDB structure files by so-called alternate locations (AltLocs). Most modeling approaches either ignore AltLocs or resolve them with simple heuristics early on during structure import. We analyzed the occurrence and usage of AltLocs in the PDB and developed an algorithm to automatically handle AltLocs in PDB files enabling all structure-based methods using rigid structures to take the alternative protein conformations described by AltLocs into consideration. A respective software tool named AltLocEnumerator can be used as a structure preprocessor to easily exploit AltLocs. While the amount of data makes it difficult to show impact on a statistical level, handling AltLocs has a substantial impact on a case-by-case basis. We believe that the inspection and consideration of AltLocs is a very valuable approach in many modeling scenarios.
在许多分子建模应用中，标准的操作流程仍然是将蛋白质视为单一的刚性结构。尽管构象灵活性的重要性已被广泛认知，但对其的处理仍然具有挑战性。即使是蛋白质的晶体结构通常也包含可变性，例如侧链取向或骨架片段的交替。这种构象变异性在 PDB 结构文件中通过所谓的替代位置（AltLocs）进行编码。大多数建模方法要么忽略 AltLocs，要么在结构导入早期就使用简单的启发式方法来解决它们。我们分析了 PDB 中 AltLocs 的出现和使用情况，并开发了一种算法，以自动处理 PDB 文件中的 AltLocs，从而使所有使用刚性结构的基于结构的方法都能够考虑 AltLocs 所描述的替代蛋白质构象。一个名为 AltLocEnumerator 的相应软件工具可用作结构预处理程序，以轻松利用 AltLocs。虽然数据量使得很难在统计层面上显示影响，但处理 AltLocs 在具体情况下会产生实质性的影响。我们认为，在许多建模场景中，检查和考虑 AltLocs 是一种非常有价值的方法。
