Successful discrimination of protein interactions

Camacho, Carlos J.; Gatchell, David W.

doi:10.1002/prot.10394

Cited by 52 publications

(45 citation statements)

References 18 publications

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“…A limitation of the server is the size of the proteins; no more than 11,999 atoms for the receptor and no more than 4,700 atoms for the ligand after minimization are allowed (Comeau et al 2004a; Comeau et al 2004b). The implementing algorithm in ClusPro has been successfully tested in blind CAPRI experiment where it has generated some of the best predictions for the given target structures (Camacho and Gatchell, 2003). …”

Section: Discussionmentioning

confidence: 99%

Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4

et al. 2008

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Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

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Section: Discussionmentioning

confidence: 99%

Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4

et al. 2008

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“…Camacho [176] used the notion of anchor residues to good effect for several CAPRI targets. Analysing side chain conformations after short MD simulations of the starting conformations allowed several hot spot interface residues to be identified as key anchor positions for the ClusPro/SmoothDock docking protocol [177]. This approach achieved 2 high accuracy, 2 medium accuracy, and 1 acceptable predictions in CAPRI rounds 3-5 [40].…”

Section: Modeling Side-chain Flexibilitymentioning

confidence: 99%

Recent Progress and Future Directions in Protein-Protein Docking

Ritchie

2008

CPPS

291

201

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This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking algorithms employ a range of efficient search and scoring strategies, including e.g. fast Fourier transform correlations, geometric hashing, and Monte Carlo techniques. These approaches can often produce a relatively small list of up to a few thousand orientations, amongst which a near-native binding mode is often observed. However, despite the use of improved scoring functions which typically include models of desolvation, hydrophobicity, and electrostatics, current algorithms still have difficulty in identifying the correct solution from the list of false positives, or decoys. Nonetheless, significant progress is being made through better use of bioinformatics, biochemical, and biophysical information such as e.g. sequence conservation analysis, protein interaction databases, alanine scanning, and NMR residual dipolar coupling restraints to help identify key binding residues. Promising new approaches to incorporate models of protein flexibility during docking are being developed, including the use of molecular dynamics snapshots, rotameric and off-rotamer searches, internal coordinate mechanics, and principal component analysis based techniques. Some investigators now use explicit solvent models in their docking protocols. Many of these approaches can be computationally intensive, although new silicon chip technologies such as programmable graphics processor units are beginning to offer competitive alternatives to conventional high performance computer systems. As cryo-EM techniques improve apace, docking NMR and X-ray protein structures into low resolution EM density maps is helping to bridge the resolution gap between these complementary techniques. The use of symmetry and fragment assembly constraints are also helping to make possible docking-based predictions of large multimeric protein complexes. In the near future, the closer integration of docking algorithms with protein interface prediction software, structural databases, and sequence analysis techniques should help produce better predictions of protein interaction networks and more accurate structural models of the fundamental molecular interactions within the cell.

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“…The server furnishes predicted 3D structure in a pdb format. Swiss PDB Viewer was used for viewing pdb files and computing the free energy of the predicted 3D structures [37,38].…”

Section: Insilico Analysismentioning

confidence: 99%

Polymorphic analysis of MC4R gene in ethnic Kashmiri population with type 2 diabetes

Dar

Rasool

Zargar

et al. 2015

Int J Diabetes Dev Ctries

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Activation of MC4R gene has been shown to inhibit appetite and increase basal metabolic rate while deficiency leads to obesity, hyperphagia, severe hyperinsulinemia, increased linear growth and decrease in metabolic activity, facts that drew strong attention as a possible cause of obesity and diabetes. In this study, we aimed to investigate the sequence variations of MC4R gene in a diabetic population of the Kashmir region and work out association of such variations (if any) with the disease phenotype. No such study has ever been taken up in the Jammu and Kashmir State, despite the existence of a significant population of type 2 diabetic patients. A total of 420 samples (200 with type 2 diabetes and 220 controls) were taken. Genomic DNA was extracted from whole blood samples using standard protocols like salting out and proteinase k. The specific fragments of DNA were amplified and hence then purified. Purified amplicons were subjected to heteroduplex assay to screen for SNPs/mutations. Samples which showed heteroduplex bands were sent for sequencing. The genotype and allele frequencies were evaluated using the χ 2 tests or the Fisher exact tests. We here report one novel heterozygous mutation, i.e. C to T at codon 7 in diabetic patients. The results showed significant differences in the 7C/ T genotype (p < 0.001) and allele (p < 0.0001) frequencies between type 2 diabetes mellitus and control subjects. The fasting blood sugar (FBS), postprandial blood sugar (PPBS) and random blood sugar (RBS) levels were higher with CT genotype in type 2 diabetes mellitus patients but difference was not found statistically significant. C to T substituting arginine with cysteine appeared to associate with type 2 diabetes in the Kashmiri population. Insilico predictions show that substitutions likely have an impact on structure and functional properties of protein making it imperative to understand their functional consequences in relation with diabetes and obesity.

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Successful discrimination of protein interactions

Cited by 52 publications

References 18 publications

Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4

Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4

Recent Progress and Future Directions in Protein-Protein Docking

Polymorphic analysis of MC4R gene in ethnic Kashmiri population with type 2 diabetes

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Successful discrimination of protein interactions

Cited by 52 publications

References 18 publications

Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

Recent Progress and Future Directions in Protein-Protein Docking

Polymorphic analysis of MC4R gene in ethnic Kashmiri population with type 2 diabetes

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Product

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Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4

Simulation of Different Truncated p16^INK4a Forms and In Silico Study of Interaction with Cdk4