Centre for Theoretical Physics & Natural Philosophy, Mahidol University, Nakhonsawan Campus, Phayuha Khiri, NakhonSawan, 60130, Thailand.
Department of Physics and Astrophysics, University of Delhi, Delhi, 110007, India.
Sci Rep. 2023 Nov 23;13(1):20626. doi: 10.1038/s41598-023-48128-y.
The Beta-lactamase protein family is vital in countering Beta-lactam antibiotics, a widely used antimicrobial. To enhance our understanding of this family, we adopted a novel approach employing a multiplex network representation of its multiple sequence alignment. Each network layer, derived from the physiochemical properties of amino acids, unveils distinct insights into the intricate interactions among nodes, thereby enabling the identification of key motifs. Nodes with identical property signs tend to aggregate, providing evidence of the presence of consequential functional and evolutionary constraints shaping the Beta-lactamase family. We further investigate the distribution of evolutionary links across various layers. We observe that polarity manifests the highest number of unique links at lower thresholds, followed by hydrophobicity and polarizability, wherein hydrophobicity exerts dominance at higher thresholds. Further, the combinations of polarizability and volume, exhibit multiple simultaneous connections at all thresholds. The combination of hydrophobicity, polarizability, and volume uncovers shared links exclusive to these layers, implying substantial evolutionary impacts that may have functional or structural implications. By assessing the multi-degree of nodes, we unveil the hierarchical influence of properties at each position, identifying crucial properties responsible for the protein's functionality and providing valuable insights into potential targets for modulating enzymatic activity.
β-内酰胺酶蛋白家族在对抗广泛使用的抗菌药物β-内酰胺抗生素方面至关重要。为了更深入地了解这个家族，我们采用了一种新的方法，即使用多重网络表示其多重序列比对。每个网络层都源自氨基酸的物理化学性质，揭示了节点之间复杂相互作用的独特见解，从而能够识别关键基序。具有相同性质符号的节点往往会聚集在一起，这表明存在重要的功能和进化限制，这些限制塑造了β-内酰胺酶家族。我们进一步研究了进化联系在不同层之间的分布。我们观察到，在较低的阈值下，极性表现出最多的独特联系，其次是疏水性和极化率，其中疏水性在较高的阈值下占主导地位。此外，极化率和体积的组合在所有阈值下都显示出多个同时的连接。疏水性、极化率和体积的组合揭示了这些层特有的共享联系，这意味着可能具有功能或结构意义的重大进化影响。通过评估节点的多重度，我们揭示了每个位置属性的层次影响，确定了对蛋白质功能负责的关键属性，并为调节酶活性的潜在目标提供了有价值的见解。
