Protein-RNA docking is still an open question. One of the main challenges is to develop an effective scoring function that can discriminate near-native structures from the incorrect ones. To solve the problem, we have constructed a knowledge-based residue-nucleotide pairwise potential with secondary structure information considered for nonribosomal protein-RNA docking. Here we developed a weighted combined scoring function RpveScore that consists of the pairwise potential and six physics-based energy terms. The weights were optimized using the multiple linear regression method by fitting the scoring function to L_rmsd for the bound docking decoys from Benchmark II. The scoring functions were tested on 35 unbound docking cases. The results show that the scoring function RpveScore including all terms performs best. Also RpveScore was compared with the statistical mechanics-based method derived potential ITScore-PR, and the united atom-based statistical potentials QUASI-RNP and DARS-RNP. The success rate of RpveScore is 71.6% for the top 1000 structures and the number of cases where a near-native structure is ranked in top 30 is 25 out of 35 cases. For 32 systems (91.4%), RpveScore can find the binding mode in top 5 that has no lower than 50% native interface residues on protein and nucleotides on RNA. Additionally, it was found that the long-range electrostatic attractive energy plays an important role in distinguishing near-native structures from the incorrect ones. This work can be helpful for the development of protein-RNA docking methods and for the understanding of protein-RNA interactions. RpveScore program is available to the public at http://life.bjut.edu.cn/kxyj/kycg/2017116/14845362285362368_1.html Proteins 2017; 85:741-752. © 2016 Wiley Periodicals, Inc.

The maltose transporter from Escherichia coli is one of the ATP-binding cassette (ABC) transporters that utilize the energy from ATP hydrolysis to translocate substrates across cellular membranes. Until 2011, three crystal structures have been determined for maltose transporter at different states in the process of transportation. Here, based on these crystal structures, the allosteric pathway from the resting state (inward-facing) to the catalytic intermediate state (outward-facing) is studied by applying an adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way. The closing of the nucleotide-binding domains occurs first, and subsequently this conformational change is propagated to the transmembrane domains (TMD) via the EAA and EAS loops, and then to the maltose-binding protein, which facilitates the translocation of the maltose. It is also found that there exist nonrigid-body and asymmetric movements in the TMD. The cytoplasmic gate may only play the role of allosteric propagation during the transition from the pretranslocation to outward-facing states. In addition, the results show that the movment of the helical subdomain towards the RecA-like subdomain mainly occurs in the earlier stages of the transition. These results can provide some insights into the understanding of the mechanism of ABC transporters.

We explored the main factors affecting the activity of compounds by different statistical and computational methods.

The transporter MsbA is a kind of multidrug resistance ATP-binding cassette transporter that can transport lipid A, lipopolysaccharides, and some amphipathic drugs from the cytoplasmic to the periplasmic side of the inner membrane. In this work, we explored the allosteric pathway of MsbA from the inward- to outward-facing states during the substrate transport process with the adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way. The large-scale closing motions of the nucleotide-binding domains occur first, accompanied with a twisting motion at the same time, which becomes more obvious in middle and later stages, especially for the later. This twisting motion plays an important role for the rearrangement of transmembrane helices and the opening of transmembrane domains on the periplasmic side that mainly take place in middle and later stages respectively. The topological structure plays an important role in the motion correlations above. The conformational changes of nucleotide-binding domains are propagated to the transmembrane domains via the intracellular helices IH1 and IH2. Additionally, the movement of the transmembrane domains proceeds in a nonrigid body, and the two monomers move in a symmetrical way, which is consistent with the symmetrical structure of MsbA. These results are helpful for understanding the transport mechanism of the ATP-binding cassette exporters.