A computational method for the prediction and functional analysis of potential <i>Mycobacterium tuberculosis</i> adhesin-related proteins

Mycobacterial adherence plays a major role in the establishment of infection within the host. Adhesin-related proteins attach to host receptors and cell-surface components. The current study aimed to utilize in-silico strategies to determine the adhesin potential of conserved hypothetical (CH) proteins. Computational analysis was performed on the whole <i>Mycobacterium tuberculosis</i> H37Rv proteome using a software program for the prediction of adhesin and adhesin-like proteins using neural networks (SPAAN) to determine the adhesin potential of CH proteins. A robust pipeline of computational analysis tools: Phyre2 and pFam for homology prediction; Mycosub, PsortB, and Loctree3 for subcellular localization; SignalP-5.0 and SecretomeP-2.0 for secretory prediction, were utilized to identify adhesin candidates. SPAAN revealed 776 potential adhesins within the whole MTB H37Rv proteome. Comprehensive analysis of the literature was cross-tabulated with SPAAN to verify the adhesin prediction potential of known adhesin (<i>n</i> = 34). However, approximately a third of known adhesins were below the probability of adhesin (P_ad) threshold (P_ad ≥0.51). Subsequently, 167 CH proteins of interest were categorized using essential in-silico tools. The use of SPAAN with supporting in-silico tools should be fundamental when identifying novel adhesins. This study provides a pipeline to identify CH proteins as functional adhesin molecules.