Biofilms have a significant role in microbial persistence, antibiotic resistance, and chronic infections; consequently, there is a pressing need for development of novel “anti-biofilm strategies.” One of the fundamental mechanisms involved in biofilm formation is protein–protein interactions of “amyloid-like proteins” (ALPs) in the extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of structural features the of protein–protein interaction with conventional structure biology tools including X-ray diffraction and nuclear magnetic resonance is technically challenging, expensive, and time-consuming. In contrast, modeling such interactions is time-efficient and economical, and might provide deeper understanding of structural basis of interactions. Although it is often acknowledged that molecular modeling methods have varying accuracy, their careful implementation with supplementary verification methods can provide valuable insight and directions for future studies. With this reasoning, during the present study, the protein–protein interaction of TasA_(28–261)–TapA_(33–253) (which is a decisive process for biofilm formation by Bacillus subtilis) was modeled using in silico approaches, viz., molecular modeling, protein–protein docking, and molecular dynamics simulations. Results obtained here identified amino acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with principal component analyses (PCA) and free energy landscape (FEL) analyses. Results presented here represent novel finding, and we hypothesize that amino acid residues identified during the present study could be targeted for inhibition of biofilm formation by B. subtilis.

中文翻译：

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TasA（28-261）-TapA（33-253）的蛋白质-蛋白质相互作用建模的计算机研究：枯草芽孢杆菌形成生物膜的决定性过程。

生物膜在微生物持久性，抗生素抗性和慢性感染中具有重要作用；因此，迫切需要开发新颖的“抗生物膜策略”。生物膜形成的基本机制之一是细胞外基质中“淀粉样蛋白”（ALP）的蛋白质-蛋白质相互作用。这种相互作用可能是开发新型抗生物膜策略的潜在目标；因此，评估这些相互作用的结构特征可能具有很大的科学价值。与传统的结构生物学工具（包括X射线衍射和核磁共振）进行蛋白质-蛋白质相互作用的结构特征表征在技术上具有挑战性，昂贵且耗时。相反，对此类交互进行建模既省时又经济，并且可以提供对交互结构基础的更深入了解。尽管人们经常承认分子建模方法的准确性各不相同，但仔细地使用补充验证方法可以为未来的研究提供有价值的见识和方向。因此，在本研究中，TasA的蛋白质相互作用_{（28–261）} –TapA _{（33–253）}（这是枯草芽孢杆菌形成生物膜的决定性过程）使用计算机模拟方法进行建模，即分子建模，蛋白质-蛋白质对接和分子动力学模拟。此处获得的结果确定了两种蛋白质的内在无序区域内存在的氨基酸残基对于相互作用至关重要。这些结果得到主成分分析（PCA）和自由能态（FEL）分析的进一步支持。此处提出的结果代表了新发现，并且我们假设在本研究中鉴定出的氨基酸残基可以靶向抑制枯草芽孢杆菌形成生物膜。