Protein-protein interactions are critically dependent on just a few residues (“hot spots”) at the interfaces. Hot
spots make a dominant contribution to the binding free energy and if mutated they can disrupt the interaction. As
mutagenesis studies require significant experimental efforts, there exists a need for accurate and reliable computational
hot spot prediction methods. Compared to the supervised hot spot prediction algorithms, the semi-supervised prediction
methods can take into consideration both the labeled and unlabeled residues in the dataset during the prediction procedure.
The transductive support vector machine has been utilized for this task and demonstrated a better prediction performance.
To the best of our knowledge, however, none of the transductive semi-supervised algorithms takes all the three semisupervised
assumptions, i.e., smoothness, cluster and manifold assumptions, together into account during learning. In this
paper, we propose a novel semi-supervised method for hot spot residue prediction, by considering all the three semisupervised
assumptions using nonlinear models. Our algorithm, IterPropMCS, works in an iterative manner. In each
iteration, the algorithm first propagates the labels of the labeled residues to the unlabeled ones, along the shortest path
between them on a graph, assuming that they lie on a nonlinear manifold. Then it selects the most confident residues as
the labeled ones for the next iteration, according to the cluster and smoothness criteria, which is implemented by a
nonlinear density estimator. Experiments on a benchmark dataset, using protein structure-based features, demonstrate that
our approach is effective in predicting hot spots and compares favorably to other available methods. The results also show
that our method outperforms the state-of-the-art transductive learning methods.
Hot spot prediction, multiple semi-supervised assumptions, nonlinear density estimator, nonlinear manifold, semisupervised
Xin Gao, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.