Structure and sequence alignment of IN and viral DNA (PDB code: 3L2T).

<p>(A) The structure of PFV IN and viral DNA. (B) The sequence alignment of the CCD for PFV and HIV-1 IN. (C) The sequence of viral DNA.</p

Correlation between the experimental IC₅₀ values and the calculated GOLD score for a series of DKAs.

<p>Correlation between the experimental IC₅₀ values and the calculated GOLD score for a series of DKAs.</p

Comparison and correlation of the experimental and calculated B-factors for the PFV IN and IN-DNA systems.

<p>(A) Experimental and calculated B-factors for PFV IN system. (B) Correlation of experimental B-factors and the calculated values for PFV IN system. (C) Experimental and calculated B-factors for PFV IN-DNA system. (B) Correlation of experimental B-factors and the calculated values for PFV IN-DNA system. The number of 10∼374 represents the id of C_а atoms for PFV IN and the number of 375∼480 denotes viral DNA. Every base is described by P, C4’ and C2 atoms. Because the 5′ end of viral DNA (i.e. A1 and T20) has no P atoms, 106 (36×3−2 = 106) is enough for defining viral DNA.</p

Structures and measured activities of a series of DKA inhibitors used for the docking study.

<p>Structures and measured activities of a series of DKA inhibitors used for the docking study.</p

The fast and slow motion modes of PFV IN and IN-DNA systems.

<p>(A) Fast motion mode of IN. (B) The first slow motion mode of IN. (C) Fast motion mode of IN-DNA. (D) The first slow motion mode of IN-DNA. The definition of residue number is the same with that of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054929#pone-0054929-g002" target="_blank">Figure 2</a>.</p

Cross-correlation map of PFV IN (A) and IN-DNA.

<p>Cross-correlation map calculated using ANM for PFV IN and IN-DNA systems are shown in panel (A) and (B), respectively. The definition of residue number is the same with that of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054929#pone-0054929-g002" target="_blank">Figure 2</a>.</p

The representative binding modes of PFV IN-DNA with four inhibitors.

<p>(A) Compound 7. (B) Compound 8. (C) Compound 13. (D) Compound 18. The same orientation is adopted for PFV IN-DNA structure.</p

The first slow motion modes of PFV IN and IN-DNA.

<p>The front and side face views for the first slow motion modes of PFV IN and IN-DNA systems are illustrated in panel (A, C) and (B, D), respectively. The slow motion modes are shown with cone model. The length of the cone is correlative with the motion magnitude and the motion direction is depicted with the orientation of the cone. The NED/NTD, CTD and CCD are denoted by three red rectangles in the sketch map.</p

TALE-DNA direct hydrogen bonds in 11.5 repeats with occupancy over 40%.

<p>Residue id* is the index of a residue in each TAL repeat sequence. The specific interactions are in bold while non-bold denotes nonspecific interactions.</p

Exploring the molecular basis of RNA recognition by the dimeric RNA-binding protein via molecular simulation methods

<p>RNA-binding protein with multiple splicing (RBPMS) is critical for axon guidance, smooth muscle plasticity, and regulation of cancer cell proliferation and migration. Recently, different states of the RNA-recognition motif (RRM) of RBPMS, one in its free form and another in complex with CAC-containing RNA, were determined by X-ray crystallography. In this article, the free RRM domain, its wild type complex and 2 mutant complex systems are studied by molecular dynamics (MD) simulations. Through comparison of free RRM domain and complex systems, it's found that the RNA binding facilitates stabilizing the RNA-binding interface of RRM domain, especially the C-terminal loop. Although both R38Q and T103A/K104A mutations reduce the binding affinity of RRM domain and RNA, the underlining mechanisms are different. Principal component analysis (PCA) and Molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods were used to explore the dynamical and recognition mechanisms of RRM domain and RNA. R38Q mutation is positioned on the homodimerization interface and mainly induces the large fluctuations of RRM domains. This mutation does not directly act on the RNA-binding interface, but some interfacial hydrogen bonds are weakened. In contrast, T103A/K104A mutations are located on the RNA-binding interface of RRM domain. These mutations obviously break most of high occupancy hydrogen bonds in the RNA-binding interface. Meanwhile, the key interfacial residues lose their favorable energy contributions upon RNA binding. The ranking of calculated binding energies in 3 complex systems is well consistent with that of experimental binding affinities. These results will be helpful in understanding the RNA recognition mechanisms of RRM domain.</p