Suryani Lukman

Khalifa University | KU

More than 20 unique diseases such as diabetes, Alzheimer’s disease, Parkinson’s disease are caused by the abnormal aggregations of pathogenic proteins such as amylin, β-amyloid (Aβ), and α-synuclein. All pathogenic proteins differ from each other in biological function, primary sequences, and morphologies; however, the proteins are toxic when aggre...

The misfolding of proteins can lead to fibrillar and non-fibrillar deposits that are the hallmark of numerous human diseases. Inhibition of protein aggregation is considered as a promising strategy for the prevention of such diseases. Here we induced the fibrillar and non-fibrillar aggregates of hen egg white lysozyme (HEWL) at acidic (pH 3) and ph...

Rab proteins represent the largest family of the Rab superfamily guanosine triphosphatase (GTPase). Aberrant human Rab proteins are associated with multiple diseases, including cancers and neurological disorders. Rab subfamily members display subtle conformational variations that render specificity in their physiological functions and can be target...

Aggregates formed by amylin (a neuroendocrine peptide hormone secreted by pancreatic β-cells) are implicated in the pathogenesis of type 2 diabetes mellitus. To understand amylin’s aggregation mechanism and discover its inhibitory drugs, we have reviewed experimental and computational studies on amylin structures and inhibitors. We have also review...

Breastfeeding benefits both infants and mothers. Nutrients in mother's milk help protect infants from multiple diseases including infections, cancers, diabetes, gastrointestinal and respiratory diseases. We performed literature mining on 31,496 mother's-milk-related abstracts from PubMed and the results suggest the need for individualized mother's...

Rab11 is an important protein subfamily in the RabGTPase family. These proteins physiologically function as key regulators of intracellular membrane trafficking processes. Pathologically, Rab11 proteins are implicated in many diseases including cancers, neurodegenerative diseases and type 2 diabetes. Although they are medically important, no previo...

Residues in and around switch 1 (residues D34-I41 in Rab1a) regions of Rab1 and Rab11. The residues of PDB entries 4FMB (B, D and F chains; Rab1a in complex with VirA), 4FMC (B and D chains; Rab1a in complex with ESPG), 4FMD (B and D chains; Rab1a in complex with ESPG) and 4FME (B and E chains; Rab1a in complex with ESPG) are colored in magenta, th...

Binding site formed by residues 99, 102, 103 and 142 in PDB entries 3TKL_A and 4FMB_D. The transparent surface of PDB entries 3TKL_A and 4FMB_D are shown in (A) and (B), respectively. The cartoon representations of 3TKL_A and 4FMB_D are shown in (C) and (D), respectively. The binding site is colored in yellow. The figures are aligned in the same or...

Ligands ZINC00084617 and ZINC13208966 that prefer GDP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of PDB entry 1OIV_A. The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxygen atoms, and blue circles denote nitrogen atoms....

Ligands ZINC15952559 and ZINC11677178 that prefer GNP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of the Rab11 structures in which they scored the best. The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxygen atoms, green...

Structures of diverse ligands that prefer GDP-bound Rab11b. The figure shows the interactions of the structurally diverse ligands (labeled) that prefer PDB entry 4OJK_A and their interactions. ZINC17465979, ZINC17465983, ZINC05462674 and ZINC05462670 are isomers. The ligand and Rab11 side chains are shown in ball-and-stick representation. Black cir...

Conformational changes of site 1 in Rab11 representative structures. Surface representations of PDB entries 1OIV_A, 1YZK_A, 4C4P_A, 4LX0_C, 4OJK_A, 4UJ5_B, 5C46_F, and 5JCZ_D are shown in (A), (B), (C), (D), (E), (F), (G) and (H), respectively. Residues 19, 20, 101, 104, 105, 108 and 111 forming site 1 are colored in green. (TIF)

Rab11 structures 1OIV_A (GDP-bound) and 4C4P_A (GNP-bound). The ligand and Rab11 side chains are shown in ball-and-stick representation. The ligand bonds are colored in purple. Hydrogen bonds are shown as green dotted lines. The Rab11 residues making nonbonded contacts with the ligand are shown as spoked arcs. The red circle and ellipses indicate p...

Switch regions of Rab11a-Rabin8 complex (PDB entry 4UJ5_A; magenta), and unbound-Rab11a-GTP (1OIW_A; yellow). Rabin8 induces conformational changes in the switch regions of Rab11a. (TIF)

Rab11 structures, their interacting partners and binding sites. Residues in Rab11 that are not conserved in Rab1 are highlighted in cyan. (DOCX)

Binding sites identified by FTMap in Rab11 representative structures. Residues of switches 1 and 2 (residues 39–46 and 68–79) are shown in bold. RabF and RabSF regions are highlighted in magenta and orange, respectively. (DOCX)

Free energy values computed by Vinardo. The table lists the free energy values computed by Vinardo for the top scoring ligands when docked at different sites in Rab11 representative structures. (DOCX)

Details on Rab11, Ras, Rab1 proteins and the initial analyses performed on Rab11 proteins. (PDF)

Results of PCA on the ensemble of 27 Rab11 structures. (TIF)

Projection of Rab11 structures onto a two-dimensional space using the locally linear embedding algorithm. (TIF)

Sequence alignment of Rab11a and Rab11b. RabF and RabSF motifs are colored in magenta and orange, respectively. (TIF)

RMSD dendrogram of Rab11 structures. (TIF)

RMSD dendrogram of switch 2 (residues A68-A79) in Rab11 structures. (TIF)

Binding sites identified by FTMap in Rab11 representative structures. Cartoon representations of Rab11 representative structures (A) 1OIV_A, (B) 1YZK_A, (C) 4C4P_A, (D) 4LX0_C and their rotated views are shown in the first and second rows, respectively. Cartoon representations of Rab11 representative structures (E) 4OJK_A, (F) 4UJ5_B, (G) 5C46_F, (...

Binding sites in PDB entry 1OIV_A. In (A), transparent surface of 1OIV_A is shown and in (B), cartoon representation of 1OIV_A is shown. In (A) and (B), the binding site formed by residues I17, T67, R72, Y80, Y81, W105, E108 and the binding site formed by residues N101, R104, W105 and E108 are colored in cyan and orange, respectively. (TIF)

Similar binding pockets in PDB entries 3TKL_A (Rab1) and 1YZK_A (Rab11). Pockets formed by residues 99, 102, 103 and 142 in Rab1 and Rab11 are colored in blue. Probes occupying identified binding sites are shown in sticks and colored yellow, blue, and red for C, N, and O atoms, respectively. (TIF)

Binding site formed by residues N101, Q104, W105 and E108 in Rab1 and the similar binding site in Rab11. The transparent surface of PDB entries 3SFV_A (Rab1) and 3TKL_A (Rab1) are shown over their secondary structures in (A) and (B), respectively. The cartoon representations of 3SFV_A and 3TKL_A are shown in (C) and (D), respectively. The binding s...

Ligands ZINC12671898 and ZINC17353914 that prefer GNP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of the Rab11 structures in which they scored the best (see Table 3). The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxyge...

Conformation of switch regions in (A) PDB entry 4UJ5_B and (B) PDB entry 5C46_F. Switch 1 and switch 2 of the PDB entries are colored in cyan and magenta, respectively. The ligands at the active sites of the structures are colored in red. The magnesium ion at the active site of the structures is shown as green spheres. Water molecules are shown as...

Multiple sequence alignment of (A) site 1 and (B) site 2 in Rab1 and Rab11. Residues conserved in three or more sequences are highlighted in green. Residues conserved only in Rab11 are highlighted in yellow. Residues conserved only in Rab1 are highlighted in cyan. (TIF)

Plots generated by NAPS server showing betweenness centrality values of residues in (A) 1OIV_A, (B) 1YZK_A, (C) 4C4P_A, (D) 4LX0_C, (E) 4OJK_A, (F) 4UJ5_B, (G) 5C46_F and (H) 5JCZ_D. X axis shows residue number and Y axis shows betweenness centrality values of residues. (TIF)

Site 1 is structurally conserved as allosteric pocket p2 in H-Ras. The figure shows Rab11 (PDB entry 1OIV_A) and H-Ras (PDB entry 2Q21_A) structures aligned in the same orientation. (A) and (B) show site 1 (colored in green) in cartoon representations of Rab11 and H-Ras. (C) and (D) show site 1 (colored in green) in surface representations of Rab11...

Residues of site 1 and site 2 that are conserved in H-Ras allosteric sites. The figure shows the sequence alignment of site 1 and site 2 residues that are contacted by small molecules during virtual screening, and the corresponding residues in H-Ras pockets p2 and p3, respectively. The residues conserved between the binding sites are highlighted in...

Vinardo scores for ligands targeting GDP-bound Rab11a (PDB entry 1OIV_A). The target sites of ligands in 1OIV_A and their free energy of binding computed by Vinardo are listed. GDP stands for Guanosine-5'-Diphosphate. (DOCX)

Vinardo scores for ligands that target GDP-bound Rab11b (PDB entry 4OJK_A). The target sites of ligands and their free energy of binding computed by Vinardo are listed. GDP stands for Guanosine-5'-Diphosphate. (DOCX)

Principal component analysis of Rab11 structures. Projection of Rab11 structures onto the first and second principal components (PCs) are shown in (A) and projection of Rab11 structures onto the first and third PCs are shown in (B). (TIF)

Projection of Rab11 structures onto the subspace defined by first and second independent components. (TIF)

RMSD dendrogram of switch 1 (residues E39-V46) in Rab11 structures. (TIF)

RMSD dendrogram of interswitch (residues E47-T67) region in Rab11 structures. (TIF)

Binding site formed by residues Y10-I17 in PDB entries 4C4P_A, 4LX0_C and 5JCZ_D. The transparent surface of PDB entries 4C4P_A, 4LX0_C and 5JCZ_D are shown in (A), (B) and (E), respectively. The cartoon representations of 4C4P_A, 4LX0_C and 5JCZ_D are shown in (C), (D) and (F), respectively. The binding site is colored in cyan. The figures are ali...

Binding site formed by residues D19, S20, G69, Q70, E71 and W105 in PDB entries 1YZK_A and 4C4P_A. The transparent surface of PDB entries 1YZK_A and 4C4P_A are shown in (A) and (B), respectively. The cartoon representations of 1YZK_A and 4C4P_A are shown in (C) and (D), respectively. The binding site is colored in orange. The figures are aligned in...

Binding site formed by residues D19, S20, G69, Q70, E71 and W105 in PDB entries 4UJ5_B, 5C46_F and 5JCZ_D. The transparent surface of PDB entries 4UJ5_B, 5C46_F and 5JCZ_D are shown over their secondary structures in (A), (B) and (E), respectively. The cartoon representations of 4UJ5_B, 5C46_F and 5JCZ_D are shown in (C), (D) and (F), respectively....

Binding site formed by residues G45, T67, A68, R74 and I76 in PDB entries 1YZK_A and 4UJ5_B. The transparent surface of PDB entries 1YZK_A and 4UJ5_B are shown over their secondary structures in (A) and (B), respectively. The cartoon representations of 1YZK_A and 4UJ5_B are shown in (C) and (D), respectively. The binding site is colored in orange....

Similar binding sites in PDB entries 2WWX_A (Rab1) and 4C4P_A (Rab11). Binding sites formed by residues 10–17 in Rab1 and Rab11 structures are shown. RabSF1 (residues 8–13) and Switch 2 (Residues 68–79) are colored in orange and pink, respectively. Probes occupying identified binding sites are shown in surface and colored yellow, blue, and red for...

Binding site formed by residues K10-S17 in PDB entries 2FOL_A and 2WWX_A. The transparent surface of PDB entries 2FOL_A and 2WWX_A are shown in (A) and (B), respectively. The cartoon representations of 2FOL_A and 2WWX_A are shown in (C) and (D), respectively. The binding site is colored in orange. The figures are aligned in the same orientation. (T...

Binding site formed by residues K10-S17 in PDB entry 4I1O_E (Rab1) and the similar binding site in PDB entry 4C4P_A (Rab11). In (A), transparent surface of PDB entry 4I1O_E is shown and in (B), cartoon representation of the PDB entry 4I1O is shown. The binding site formed by residues K10-S17is colored in orange in (A) and (B). In (C), the similar b...

Ligands ZINC04720972 and ZINC11677172 that prefer GDP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of PDB entry 1OIV_A. ZINC11677172 also has interactions with a sulfate ion present near its binding site in the target structure. The ligand and Rab11 side chains are shown in ball-and-stick representation...

Ligands ZINC00393674 and ZINC01701460 that prefer GDP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of PDB entry 1OIV_A. The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxygen atoms, green circles denote chlorine atoms and...

Ligands ZINC29590275 and ZINC01726776 that prefer GNP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of the Rab11 structures in which they scored the best. The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxygen atoms, yello...

Conformational changes of site 2 in Rab11 representative structures. Surface representations of PDB entries 1OIV_A, 1YZK_A, 4C4P_A, 4LX0_C, 4OJK_A, 4UJ5_B, 5C46_F and 5JCZ_D are shown in (A), (B), (C), (D), (E), (F), (G) and (H), respectively. Residues 106, 109, 110, 113, 117, 118, 119, 148, 149 and 171 forming site 2 are colored in blue. (TIF)

Switch regions of Rab11a-Myosin 5a complex (PDB entries 5JCZ_A; green), Rab11a-Myosin 5b complex (PDB entries 4LX0_A; orange) and unbound-Rab11a-GTP (1OIW_A; yellow). Residue S40 adopts different orientations in the structures. Switch 1 and switch 2 adopt different conformations from those of unbound-Rab11a. (TIF)

Switch regions of Rab11a-P14KB complex (PDB entry 4DOL_B; red), and unbound-Rab11a-GTP (1OIW_A; yellow). P14KB induces conformational changes in the switch regions of Rab11a. Unlike the observations on residue S40 in other protein complexes used in our study, residue S40 adopts a conformation similar to that in unbound-Rab11a-GTP. (TIF)

Vinardo scores for ligands that target GNP-bound conformations of Rab11a. The target sites of ligands, and their free energy of binding computed by Vinardo are listed. GNP stands for Phosphoaminophosphonic acid-guanylate ester. (DOCX)

Sequence identities of Rab sequences. Sequence identities of Rab1a, Rab1b, Rab11a and Rab11b as computed by Clustal Omega are shown above. (DOCX)

Shortest paths from residues in site 1 and site 2 to the nucleotide-binding site in Rab11. The table above lists the shortest paths from site 1 and site 2 to the nucleotide binding site, that are observed to have minimal length during network analysis. The second column of the table shows the PDB entries for which such shortest paths are observed a...

Sequence alignments of Rab1 and Rab11 sequences. (PDF)

Figures showing interactions of various ligands with Rab11. (PDF)

Residue S40 in PDB entry 2D7C_A (Rab11 in complex with FIP2; magenta) and residue Y40 in PDB entries 3TKL_A (Rab1a-GTP in complex with LidA; red) and 3SFV_A(Rab1a-GDP in complex with LidA; green) are labeled. (TIF)

Binding sites in PDB entries 1OIV_A and 1YZK_A. The figure shows the binding site formed by residues Y99, F142, V102 and E103 (colored in orange) in PDB entries 1OIV_A ((A) and (C)) and 1YZK_A ((B) and (D)). The top panel shows the transparent surface of the PDB entries and the bottom panel shows the cartoon representation of the PDB entries, align...

Binding site formed by residues Y8-K13 and Y173-I175 in PDB entry 1YZK_A. In (A), transparent surface of 1YZK_A is shown and in (B), cartoon representation of 1YZK_A is shown. The binding site is colored in orange. The figures are aligned in the same orientation. (TIF)

Binding site formed by residues D19, S20, G69, Q70, E71 and W105 in PDB entries 4LX0_C and 4OJK_A. The transparent surface of PDB entries 4LX0_C and 4OJK_A are shown in (A) and (B), respectively. The cartoon representations of 4LX0_C and 4OJK_A are shown in (C) and (D), respectively. The binding site is colored in orange. The figures are aligned in...

Binding site formed by residues S25-S42 and T43-E47 in PDB entry 4UJ5_B. In (A), transparent surface of 4UJ5_B is shown and in (B), cartoon representation of 4UJ5_B is shown. The binding site is colored in orange. The figures are aligned in the same orientation. (TIF)

Binding site formed by residues 99, 102, 103 and 142 in PDB entry 4I1O_E (Rab1) and the similar binding site in PDB entry 1OIV_A (Rab11). In (A), transparent surface of PDB entry 4I1O_E is shown and in (B), cartoon representation of the PDB entry is shown. The binding site formed by residues V99, W102, L103 and S142 in 4I1O_E is colored in yellow i...

Residues 8–13 in Rab1 and Rab11 that form binding sites. The transparent surface of PDB entries 2WWX_A (Rab1), 3SFV_A (Rab1) and, 4I1O_E (Rab1) are shown in (A), (B) and (C), respectively. The cartoon representations of 2WWX_A, 3SFV_A and 4I1O_E are shown in (D), (E) and (F), respectively. Residues 8–13 in Rab1 is colored in orange in (A)-(F). In (...

Binding site in Rab1 which is not observed in Rab11. The binding site in Rab1 (PDB entry 2FOL_A) formed by residues L25-D31, which is not observed in any Rab11 representatives, is colored in yellow in its (A) transparent surface and (B) cartoon representation. (TIF)

Ligands ZINC01573829 and ZINC01577889 that prefer GNP-bound Rab11a. The figure shows the interactions of the ligands (labeled) with the residues of the Rab11 structures in which they scored the best (see Table 3). The ligand and Rab11 side chains are shown in ball-and-stick representation. Black circles denote carbon atoms, red circles denote oxyge...

Ligands docked at PDB entries (A) 5C46_F and (B) 5JCZ_D. Ligands (A) ZINC29590257 and (B) ZINC01568793 are shown in brown sticks. Residues of site 1 are colored in green and ligands are shown as brown sticks. In 5C46_F, ligands interact with a small cavity formed by residues H99, L100 and A142 which are colored in cyan. (TIF)

Site 2 is structurally conserved as allosteric pocket p3 in H-Ras. The figure shows Rab11 (PDB entry 1OIV_A) and H-Ras (PDB entry 2Q21_A) structures aligned in the same orientation. (A) and (B) show site 2 (colored in blue) in cartoon representations of Rab11 and H-Ras. (C) and (D) show site 2 (colored in blue) in surface representations of Rab11 a...

Pairwise sequence alignment of Rab11a and H-Ras sequences. Helix α2 (residues Y64-G77) in H-Ras and the corresponding amino acid sequences in the PSA are indicated in magenta color. Residues of helix α3 (I93-V103) and residues D105-V109 and residues S136-P140 that line pocket p3 in H-Ras and the corresponding residues in the PSA that line sites 1 a...

Switch and interswitch regions of Rab11a-FIP complexes (PDB entries 2GZD_A, 2GZD_B, 2GZH_A, 4C4P_A, 2D7C_A, 2D7C_B, 2HV8_A, 2HV8_B, 2HV8_C, 4UJ3_A and 4UJ3_G; cyan) and unbound-Rab11a-GTP (PDB entry 1OIW_A; yellow). Residue S40 that adopts different orientations in the structures is labeled. Switch 1 region of these Rab11a-FIP complexes are similar...

Rab11 structures in the ensemble of 27 structures. For each Rab11 structure in the ensemble, the experimental technique used for determining the structure, its resolution and its ligands are listed. GSP stands for 5'-Guanosine-Diphosphate-Monothiophosphate, MG stands for Magnesium ion, GNP stands for Phosphoaminophosphonic acid-guanylate ester, SO4...

Rab1 structures, their interacting partners and binding sites. Residues in Rab1 that are not conserved in Rab11 are highlighted in cyan. (DOCX)

Residues in site 1 and site 2 of Rab11 representative structures that have high betweenness centrality and their values, as computed by NAPS server. (DOCX)

Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable non-active sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologi...

Targeting non-native-ligand binding sites for potential investigative and therapeutic applications is an attractive strategy in proteins that share common native ligands, as in Rab1 protein. Rab1 is a subfamily member of Rab proteins, which are members of Ras GTPase superfamily. All Ras GTPase superfamily members bind to native ligands GTP and GDP,...

Insulin-degrading enzyme (IDE) plays critical roles in proteolysis of diverse substrates, like insulin and amyloid β. Pathologically, IDE is implicated in type 2 diabetes mellitus and Alzheimer’s diseases, but potent and selective regulators of IDE remain elusive. We have applied structural bioinformatics techniques to the largest ensemble of IDE s...

BET proteins are epigenetic readers whose deregulation results in cancer and inflammation. We show that BET proteins (BRD2, BRD3, BRD4 and BRDT) are globally similar with subtle differences in the sequences and structures of their N-terminal bromodomain. Principal component analysis and non-negative matrix factorization reveal distinct structural c...

R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor groove of DNA. Earlier nuclear magnetic resonance studies indicated that the R248Q mutation resulted in conformation changes in parts of DBD far from the mutation site. However, how information propagates from the mutation site to the rest of the DBD is still not well und...

To lower blood glucose concentration, insulin binds to insulin receptor (IR) that possesses two distinct insulin binding sites to trigger downstream signaling events leading to an increased uptake of glucose into muscle and fat cells. Comprehensive understandings of structural and dynamic mechanisms of insulin and its receptor are essential to desi...

Molecular recognition in biological systems relies on the existence of specific attractive interactions between two partner molecules. Structure-based drug design seeks to identify and optimize such interactions between ligands and their protein targets. The approach followed in medicinal chemistry follows a combination of careful analysis of struc...

The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD). In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8...

Actionable 3D subspace clustering from real-world continuous-valued 3D (i.e., object-attribute-context) data promises tangible benefits such as discovery of biologically significant protein residues and profitable stocks, but existing algorithms are inadequate in solving this clustering problem; most of them are not actionable (ability to suggest p...

Capping protein (CP) is important for the regulation of actin polymerization. CP binds to the barbed end of the actin filament and prevents actin polymerization. This interaction is modulated through competitive binding by regulatory proteins such as myotrophin (V-1) and the capping protein interacting (CPI) motif from CARMIL. The binding site of m...

Ensemble fragment mapping results highlight three non-nucleotide binding sites. Representative Ras crystal structure conformers (gray protein cartoon) are shown along with the nucleotide-binding site (red molecular surface representation) and new potential binding sites p1, p2 and p3 (in pink, green and blue molecular surface representations respec...

Representative structure obtained from analyzing the Ras crystallographic ensemble. (DOC)

Aberrant Ras activity is a hallmark of diverse cancers and developmental diseases. Unfortunately, conventional efforts to develop effective small molecule Ras inhibitors have met with limited success. We have developed a novel multi-level computational approach to discover potential inhibitors of previously uncharacterized allosteric sites. Our app...

The DCCM of GDP-bound H-Ras A59G MD simulation that achieved a spontaneous GTP-to-GDP transition. (0.11 MB TIF)

Pseudo alpha Carbon torsion angle differences in MD conformers at different time point with respect to crystal structure of (A) GTP-analog-bound, (B) GDP-bound H-Ras A59G crystal conformers. Absolute values of the difference are plotted with secondary structures schematically depicted in black for helices and grey for strands. (0.12 MB TIF)

Principal component based mapping of Ras crystallographic structures. Structures are colored by nucleotide state, triphosphate in red and diphosphate in green and labeled with their PDB code where space permits. Dashed ovals represent the grouping obtained from hierarchical clustering of the projected structures in the PC1 to PC3 planes. Insert: ei...

The GTP-to-GDP transition observed in the MD trajectory of H-Ras A59G. The N-terminal (residue 65–67) of α 2 helix unwinds. Important residues 37 (pink), 60 (black), 61 (red-brown), 64 (orange), 66 (magenta, to aid unwinding visualization), 68 (blue), and 71 (green), are highlighted in CPK style.URL: http://mccammon.ucsd.edu/~lukman/movie1_24May10....

Time evolution of Cα atom RMSD from the initial structure of each simulation. Each row corresponds to a single system namely: (A and B) wtGTP, (C and D) wtGDP, (E and F) mutantGDP. Regular MD simulations are depicted in the left panel (A, C, and E,) whilst aMD simulations are depicted on the right (B, D, and F). Simulations with a bound GDP are plo...

Root mean square deviations (RMSD) of switch 1 (residues 25–40, blue), switch 2 (residues 57–75, red), switch 3 (residues 47–49, 161–165, green) of H-Ras, K-Ras, and H-Ras A59G in three sets of MD trajectories of (A) wild-type H-Ras, (B) wild-type K-Ras, (C) H-Ras A59G. (0.73 MB TIF)

Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and...

The giant protein titin, which comprises immunoglobulin (Ig) domains, acts as a bidirectional spring in muscle. The unfolding of Ig domains has been extensively studied, but their dynamics under native states have not been well-characterized. We performed molecular dynamics simulation on a single titin Ig domain and multi-domains. Mobile regions di...

The maltose transporter of Escherichia coli is a member of the ATP-binding cassette (ABC) transporter superfamily. The crystal structures of maltose transporter MalK have been determined for distinct conformations in the presence and absence of the ligand ATP, and other interacting proteins. Using the distinct MalK structures, normal mode analysis...

To assess the physico-chemical characteristics of protein-protein interactions, protein sequences and overall structural folds have been analyzed previously. To highlight this, discovery and examination of amino acid patterns at the binding sites defined by structural proximity in 3-dimensional (3D) space are essential. In this paper, we investigat...

Traditional Chinese Medicine (TCM) has been actively researched through various approaches, including computational techniques. A review on basic elements of TCM is provided to illuminate various challenges and progresses in its study using computational methods. Information on various TCM formulations, in particular resources on databases of TCM f...