Protein–protein docking with interface residue restraints*

Abstract

The prediction of protein–protein complex structures is crucial for fundamental understanding of celluar processes and drug design. Despite significant progresses in the field, the accuracy of ab initio docking without using any experimental restraints remains relatively low. With the rapid advancement of structural biology, more and more information about binding can be derived from experimental data such as NMR experiments or chemical cross-linking. In addition, information about the residue contacts between proteins may also be derived from their sequences by using evolutionary analysis or deep learning. Here, we propose an efficient approach to incorporate interface residue restraints into protein–protein docking, which is named as HDOCKsite. Extensive evaluations on the protein–protein docking benchmark 4.0 showed that HDOCKsite significantly improved the docking performance and obtained a much higher success rate in binding mode predictions than original ab initio docking.

Exploring protein-protein interactions at the proteome level

“…Although the template-free docking, the so-called ab initio docking, can yield good models of protein complexes, it is usually computationally costly since it requires extensive sampling and can often become trapped in local minima. The use of prior experimental and computational knowledge can dramatically reduce the search space and thereby improve the accuracy of both these approaches (Li and Huang, 2021). Methods that predict the binding interfaces of individual proteins can be of great use in this respect (Table S1).…”

Protein language model-embedded geometric graphs power inter-protein contact prediction

“…Therefore, it is necessary to develop computational methods to predict protein complex structures ( Bonvin, 2006 ). Predicting contacting residue pairs between interacting proteins can be considered an intermediate step for protein complex structure prediction ( Hopf et al, 2014 ; Ovchinnikov et al, 2014 ) as the predicted contacts can be integrated into protein–protein docking algorithms to assist protein complex structure prediction ( Dominguez et al, 2003 ; Li and Huang, 2021 ; Sun et al, 2020 ). Besides, the predicted contacts can also be very useful to guide protein interfacial design ( Martino et al, 2021 ) and the inter-protein contact prediction methods can be further extended to predict novel PPIs ( Cong et al, 2019 ; Green et al, 2021 ).…”

Protein language model embedded geometric graphs power inter-protein contact prediction

“…Therefore, it is necessary to develop computational methods to predict protein complex structures (Bonvin, 2006). Predicting contacting residue pairs between interacting proteins can be considered as an intermediate step for protein complex structure prediction (Hopf et al, 2014;Ovchinnikov et al, 2014), as the predicted contacts can be integrated into protein-protein docking algorithms to assist protein complex structure prediction (Dominguez et al, 2003;H. Li & Huang, 2021;Sun et al, 2020).…”

“…Therefore, it is necessary to develop computational methods to predict protein complex structures(Bonvin, 2006). Predicting contacting residue pairs between interacting proteins can be considered as an intermediate step for protein complex structure prediction(Hopf et al, 2014; Ovchinnikov et al, 2014), as the predicted contacts can be integrated into protein-protein docking algorithms to assist protein complex structure prediction(Dominguez et al, 2003; H. Li & Huang, 2021; Sun et al, 2020). Besides, the predicted contacts can also be very useful to guide protein interfacial design(Martino et al, 2021) and the inter-protein contact prediction methods can be further extended to predict novel PPIs (Cong et al, 2019; Green et al, 2021).…”