Although Schaadt et al. have previously developed models to predict the substrate specificity of Gefitinib transporters for A. thaliana proteins, one limitation of their models is that only 61 proteins were used in the training dataset for model development. Chen et al. have developed models to predict the substrate specificity for electron transporters, protein/mRNA transporters, ion transporters, and other transporters, and more recently improved this method to differentiate transporters from non-transporters using a probability distribution function for each query protein. This improved method, which is essentially a combination of the original Chen et al. model and the Ou et al. model, is limited in that the proposed threshold of 0.65 is not reliable for the prediction of transporters. Barghash et al. model is also limited to classifying transporters of only four substrates and at TC family/subfamily level. The models developed in the present study can simultaneously predict whether a query protein is a transporter or non-transporter protein and its substrate specificity for seven transporter protein classes. One advantage of our model is that it can differentiate cation and anion transporters. Our PSSM-based model demonstrated superior performance with respect to substrate specificity prediction. However, this model was computationally demanding when the PSSM profile was generated from the UniRef90 database. We observed that our TrSSP web server would take approximately 6–15 minutes per sequence to run when the UniRef90 database was used for PSSM generation. To significantly reduce the PSSM computational time, we implemented parallel computing for PSSM generation and used the UniProt/ SwissProt database as the reference database, which reduced the runtime of our TrSSP server to approximately 10 minutes for approximately 200 sequences with no impact on model performance. During vaginal transmission of HIV-1, virions in semen must traverse the thin layer of cervicovaginal mucus coating the vaginal epithelium before they can encounter and potentially infect target cells. Due to the presence of substantial quantities of secreted and transudated antibodies, CVM possesses both diffusional and immunological barrier properties against sexually transmitted viruses. In women with healthy vaginal microflora, lactobacilli secrete substantial levels of lactic acid, producing an acidic environment that inactivates leukocytes within minutes. Thus, few immune cells capable of opsonization and antibody-dependent cell-mediated cytotoxicity are actually present in healthy CVM secretions, which also exhibit limited complement activity. Neutralization, a process in which secreted or topically-applied Ab engage the gp120/gp41 trimeric glycoproteins on HIV at sufficient stoichiometry to preclude their attachment to target cells, is thus generally thought to be a critical component of sterilizing immunity against initial HIV infections in the vagina. Effective neutralization in the vaginal lumen that directly reduces the rates of acquiring initial infections, rather than attempting to clear infections, may be especially important since HIV infections remain difficult to cure.