ColBuilder：交联胶原纤维的灵活结构生成

ColBuilder: flexible structure generation of crosslinked collagen fibrils.

作者信息

Monego Debora, Brosz Matthias, Buck Johanna, Viliuga Vsevolod, Greicius Paulius, Jung Jaewoon, Stuehn Torsten, Schmies Matthias, Sugita Yuji, Gräter Frauke

机构信息

Max Planck Institute for Polymer Research, Mainz 55128, Germany.

Heidelberg Institute for Theoretical Studies, Heidelberg 69117, Germany.

出版信息

Bioinformatics. 2025 Jun 2;41(6). doi: 10.1093/bioinformatics/btaf278.

DOI:10.1093/bioinformatics/btaf278

PMID:40323309

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12148304/

Abstract

MOTIVATION

Collagen fibrils are fundamental building blocks of connective tissues, yet generating accurate molecular models of their structure remains challenging due to their hierarchical organization and complex crosslinking patterns.

RESULTS

ColBuilder has been developed to automate the generation of atomistic models of crosslinked collagen fibrils and facilitate the setup of molecular simulations. The tool integrates homology modeling, higher order structure generation and optimization to build complete fibril structures with precise control over sequence composition, crosslinking patterns, and dimensions. Users can explore different collagen sequences, manipulate crosslink chemistry through mixed ratios and densities, and generate fibrils of varying diameter and length. All-atom molecular dynamics simulations of 335nm-long fibrils validate the generated structures, showing excellent agreement with experimental measurements of D-band periodicity and force-extension behavior.

AVAILABILITY AND IMPLEMENTATION

ColBuilder is available both as an open-source command-line application and through a web interface at https://colbuilder.mpip-mainz.mpg.de.

摘要

动机

胶原纤维是结缔组织的基本组成部分，但由于其层次结构和复杂的交联模式，生成其结构的精确分子模型仍然具有挑战性。

结果

已开发出ColBuilder，用于自动生成交联胶原纤维的原子模型，并便于设置分子模拟。该工具整合了同源建模、高阶结构生成和优化，以构建完整的纤维结构，并能精确控制序列组成、交联模式和尺寸。用户可以探索不同的胶原序列，通过混合比例和密度操纵交联化学，并生成不同直径和长度的纤维。对335nm长纤维的全原子分子动力学模拟验证了生成的结构，与D波段周期性和力-伸长行为的实验测量结果显示出极好的一致性。