DINE: A Novel Score Function for Modeling Multidomain Protein Structures with Domain Linker and Interface Restraints

Abstract

The functional sites of multidomain proteins are often found at the interfaces of two or more domains. Therefore, the spatial arrangement of the domains is essential in understanding the functional mechanisms of multidomain proteins. However, an experimental determination of the whole structure of a multidomain protein is often difficult due to flexibility in inter-domain arrangement. We have developed a score function, named DINE, to detect probable docking poses generated in a rigid-body docking simulation. This score function takes into account the binding energy, information about the domain interfaces of homologous proteins, and the end-to-end distance spanned by the domain linker. We have examined the performance of DINE on 55 non-redundant known structures of two-domain proteins. In the results, the near-native docking poses were scored within the top 10 in 65.5% of the test cases. DINE scored the near-native poses higher in comparison with an existing domain assembly method, which also used binding energy and linker distance restraints. The results demonstrate that the domain-interface restraints of DINE are quite efficient in selecting near-native domain assemblies.