Table_5_AMPing Up the Search: A Structural and Functional Repository of Antimicrobial Peptides for Biofilm Studies, and a Case Study of Its Application to Corynebacterium striatum, an Emerging Pathogen.docx

Antimicrobial peptides (AMPs) have been recognized for their ability to target processes important for biofilm formation. Given the vast array of AMPs, identifying potential anti-biofilm candidates remains a significant challenge, and prompts the need for preliminary in silico investigations prior to extensive in vitro and in vivo studies. We have developed Biofilm-AMP (B-AMP), a curated 3D structural and functional repository of AMPs relevant to biofilm studies. In its current version, B-AMP contains predicted 3D structural models of 5544 AMPs (from the DRAMP database) developed using a suite of molecular modeling tools. The repository supports a user-friendly search, using source, name, DRAMP ID, and PepID (unique to B-AMP). Further, AMPs are annotated to existing biofilm literature, consisting of a vast library of over 10,000 articles, enhancing the functional capabilities of B-AMP. To provide an example of the usability of B-AMP, we use the sortase C biofilm target of the emerging pathogen Corynebacterium striatum as a case study. For this, 100 structural AMP models from B-AMP were subject to in silico protein-peptide molecular docking against the catalytic site residues of the C. striatum sortase C protein. Based on docking scores and interacting residues, we suggest a preference scale using which candidate AMPs could be taken up for further in silico, in vitro and in vivo testing. The 3D protein-peptide interaction models and preference scale are available in B-AMP. B-AMP is a comprehensive structural and functional repository of AMPs, and will serve as a starting point for future studies exploring AMPs for biofilm studies. B-AMP is freely available to the community at https://b-amp.karishmakaushiklab.com and will be regularly updated with AMP structures, interaction models with potential biofilm targets, and annotations to biofilm literature.

抗菌肽（Antimicrobial Peptides，AMPs）已被证实可靶向生物膜形成过程中的关键环节。鉴于抗菌肽种类繁多，筛选潜在抗生物膜候选肽仍面临巨大挑战，因此在开展大规模体外实验（in vitro）及体内实验（in vivo）前，有必要先进行计算机模拟实验（in silico）的预实验研究。
本研究构建了生物膜抗菌肽数据库（Biofilm-AMP，简称B-AMP），这是一套经过人工整理的、收录与生物膜研究相关的抗菌肽三维结构与功能信息的资源库。当前版本的B-AMP收录了来自DRAMP数据库的5544条抗菌肽的预测三维结构模型，这些模型通过一系列分子建模工具构建完成。该数据库支持便捷的多维度检索，可通过来源、名称、DRAMP ID以及B-AMP专属标识符PepID进行查询。此外，数据库针对现有超1万篇生物膜相关文献对收录的抗菌肽进行了注释，进一步拓展了B-AMP的功能维度。
为展示B-AMP的实用价值，本研究以新兴致病菌纹状棒杆菌（Corynebacterium striatum）的生物膜靶点分选酶C为例开展案例研究。基于该案例，我们从B-AMP中选取100个抗菌肽结构模型，针对纹状棒杆菌分选酶C蛋白的催化位点残基开展了计算机模拟实验（in silico）的蛋白质-肽分子对接实验。基于对接得分与相互作用残基分析，本研究提出了一套偏好排序量表，可用于筛选候选抗菌肽以开展后续计算机模拟实验（in silico）、体外实验（in vitro）及体内实验（in vivo）。B-AMP中已收录相关三维蛋白质-肽相互作用模型及上述偏好排序量表。
B-AMP是一套全面的抗菌肽结构与功能数据库，可作为未来开展生物膜相关抗菌肽研究的重要起点。B-AMP可通过https://b-amp.karishmakaushiklab.com免费向科研社群开放，后续将定期更新收录抗菌肽结构、潜在生物膜靶点相互作用模型及生物膜相关文献注释等内容。