Dataset Information

ECMIS: computational approach for the identification of hotspots at protein-protein interfaces.

ABSTRACT: BACKGROUND: Various methods have been developed to computationally predict hotspot residues at novel protein-protein interfaces. However, there are various challenges in obtaining accurate prediction. We have developed a novel method which uses different aspects of protein structure and sequence space at residue level to highlight interface residues crucial for the protein-protein complex formation. RESULTS: ECMIS (Energetic Conservation Mass Index and Spatial Clustering) algorithm was able to outperform existing hotspot identification methods. It was able to achieve around 80% accuracy with incredible increase in sensitivity and outperforms other existing methods. This method is even sensitive towards the hotspot residues contributing only small-scale hydrophobic interactions. CONCLUSION: Combination of diverse features of the protein viz. energy contribution, extent of conservation, location and surrounding environment, along with optimized weightage for each feature, was the key for the success of the algorithm. The academic version of the algorithm is available at http://caps.ncbs.res.in/download/ECMIS/ECMIS.zip.

SUBMITTER: Shingate P

PROVIDER: S-EPMC4177600 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ECMIS: computational approach for the identification of hotspots at protein-protein interfaces.

Shingate Prashant P Manoharan Malini M Sukhwal Anshul A Sowdhamini Ramanathan R

BMC bioinformatics 20140916

<h4>Background</h4>Various methods have been developed to computationally predict hotspot residues at novel protein-protein interfaces. However, there are various challenges in obtaining accurate prediction. We have developed a novel method which uses different aspects of protein structure and sequence space at residue level to highlight interface residues crucial for the protein-protein complex formation.<h4>Results</h4>ECMIS (Energetic Conservation Mass Index and Spatial Clustering) algorithm ...[more]

PMID: 25228146

Similar Datasets

Project description:BACKGROUND:Modeling protein-protein interactions (PPIs) using docking algorithms is useful for understanding biomolecular interactions and mechanisms. Typically, a docking algorithm generates a large number of docking poses, and it is often challenging to select the best native-like pose. A further challenge is to recognize key residues, termed as hotspots, at protein-protein interfaces, which contribute more in stabilizing a protein-protein interface. RESULTS:We had earlier developed a computer algorithm, called PPCheck, which ascribes pseudoenergies to measure the strength of PPIs. Native-like poses could be successfully identified in 27 out of 30 test cases, when applied on a separate set of decoys that were generated using FRODOCK. PPCheck, along with conservation and accessibility scores, was able to differentiate 'native-like and non-native-like poses from 1883 decoys of Critical Assessment of Prediction of Interactions (CAPRI) targets with an accuracy of 60%. PPCheck was trained on a 10-fold mixed dataset and tested on a 10-fold mixed test set for hotspot prediction. We obtain an accuracy of 72%, which is in par with other methods, and a sensitivity of 59%, which is better than most existing methods available for hotspot prediction that uses similar datasets. Other relevant tests suggest that PPCheck can also be reliably used to identify conserved residues in a protein and to perform computational alanine scanning. CONCLUSIONS:PPCheck webserver can be successfully used to differentiate native-like and non-native-like docking poses, as generated by docking algorithms. The webserver can also be a convenient platform for calculating residue conservation, for performing computational alanine scanning, and for predicting protein-protein interface hotspots. While PPCheck can differentiate the generated decoys into native-like and non-native-like decoys with a fairly good accuracy, the results improve dramatically when features like conservation and accessibility are included. The method can be successfully used in ranking/scoring the decoys, as obtained from docking algorithms.

Dataset Information

ECMIS: computational approach for the identification of hotspots at protein-protein interfaces.

Publications

ECMIS: computational approach for the identification of hotspots at protein-protein interfaces.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure