CLICK—topology-independent comparison of biomolecular 3D structures

Abstract

Our server, CLICK: http://mspc.bii.a-star.edu.sg/click, is capable of superimposing the 3D structures of any pair of biomolecules (proteins, DNA, RNA, etc.). The server makes use of the Cartesian coordinates of the molecules with the option of using other structural features such as secondary structure, solvent accessible surface area and residue depth to guide the alignment. CLICK first looks for cliques of points (3–7 residues) that are structurally similar in the pair of structures to be aligned. Using these local similarities, a one-to-one equivalence is charted between the residues of the two structures. A least square fit then superimposes the two structures. Our method is especially powerful in establishing protein relationships by detecting similarities in structural subdomains, domains and topological variants. CLICK has been extensively benchmarked and compared with other popular methods for protein and RNA structural alignments. In most cases, CLICK alignments were statistically significantly better in terms of structure overlap. The method also recognizes conformational changes that may have occurred in structural domains or subdomains in one structure with respect to the other. For this purpose, the server produces complementary alignments to maximize the extent of detectable similarity. Various examples showcase the utility of our web server.

Nup358 binds to AGO proteins through its SUMO ‐interacting motifs and promotes the association of target mRNA with miRISC

“…The other possibility included that there could be regions in AGO proteins that are structurally similar to the regions in SUMO that are involved in interaction with SIM [74]. Using a recently developed algorithm, CLICK, probable regions on AGO2 were recognized by structural similarity to the SUMO regions that interact with SIM [75,76]. This structural analysis identified three distinct regions on AGO2 (Fig 6F).…”

“…The chosen SUMO structure was in complex with the SIM1 of Nup358. Structural superimpositions were performed using the CLICK program [75,76] that identifies similar sub-structures regardless of topology. All superimpositions were carried out with full-length AGO2 and a truncated SUMO molecule comprising the residues 20-54 and 86-91.…”

Energetics and Dynamics Across the Bcl-2-Regulated Apoptotic Pathway Reveal Distinct Evolutionary Determinants of Specificity and Affinity

“…The core fold has 85-95 % structural overlap (Nguyen et al, 2011) across deposited structures in the PDB (Berman et al, 2000), and contains highly conserved regions including an invariant NWGR motif at the beginning of helix 5 , and a conserved hydrophobic core which maintains the tryptophan in its position ( Figure 1A). …”

Substrate-induced domain movement in a bifunctional protein, DcpA, regulates cyclic di-GMP turnover: Functional implications of a highly conserved motif

“…For the modeling studies, the DcpA protein sequence was submitted to I-TASSER server (http://zhanglab.ccmb.med.umich.edu/I-TASSER), and the generated model was structurally aligned with the known crystal structures, and compared using CLICK server (data not shown) (57). The Consurf server (http://consurf.tau.ac.il) was used to identify the structural and functional evolution of amino acids (31).…”