Department of Biotechnology, School of Life Sciences, Central University of Rajasthan - Kishangarh, Ajmer, 305817, Rajasthan, India.
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan - Kishangarh, Ajmer, 305817, Rajasthan, India.
J Mol Model. 2020 Aug 10;26(9):226. doi: 10.1007/s00894-020-04507-0.
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-TapA (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.
生物膜在微生物持久性、抗生素耐药性和慢性感染中起着重要作用；因此，迫切需要开发新的“抗生物膜策略”。生物膜形成涉及的一个基本机制是细胞外基质中“类淀粉样蛋白”(ALP)的蛋白质-蛋白质相互作用。这些相互作用可能是开发新的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具有重要的科学价值。使用传统的结构生物学工具，包括 X 射线衍射和核磁共振，对蛋白质-蛋白质相互作用的结构特征进行表征在技术上具有挑战性、昂贵且耗时。相比之下，建模这些相互作用是高效和经济的，并且可以提供对相互作用结构基础的更深入理解。尽管人们通常承认分子建模方法的准确性存在差异，但通过补充验证方法仔细实施这些方法可以为未来的研究提供有价值的见解和方向。基于此，在本研究中，使用计算方法（即分子建模、蛋白质-蛋白质对接和分子动力学模拟）对枯草芽孢杆菌 TasA-TapA（这是生物膜形成的决定性过程）的蛋白质-蛋白质相互作用进行了建模。这里获得的结果确定了两种蛋白质中内在无序区域内存在的氨基酸残基对相互作用至关重要。这些结果进一步得到主成分分析（PCA）和自由能景观（FEL）分析的支持。这里提出的结果是新的发现，我们假设在本研究中鉴定的氨基酸残基可以作为抑制枯草芽孢杆菌生物膜形成的靶点。
