MutaBind estimates and interprets the effects of sequence variants on protein–protein interactions

Proteins engage in highly selective interactions with their macromolecular partners. Sequence variants that alter protein binding affinity may cause significant perturbations or complete abolishment of function, potentially leading to diseases. There exists a persistent need to develop a mechanistic...

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Published inNucleic acids research Vol. 44; no. W1; pp. W494 - W501
Main Authors Li, Minghui, Simonetti, Franco L., Goncearenco, Alexander, Panchenko, Anna R.
Format Journal Article
LanguageEnglish
Published England Oxford University Press 08.07.2016
Subjects
Algorithms
Binding Sites
Datasets as Topic
Evolution, Molecular
Genetic Fitness
Humans
Internet
Molecular Dynamics Simulation
Neoplasms - genetics
Protein Binding - genetics
Protein Interaction Mapping - methods
Protein Interaction Maps - genetics
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Software
Web Server issue
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Summary:Proteins engage in highly selective interactions with their macromolecular partners. Sequence variants that alter protein binding affinity may cause significant perturbations or complete abolishment of function, potentially leading to diseases. There exists a persistent need to develop a mechanistic understanding of impacts of variants on proteins. To address this need we introduce a new computational method MutaBind to evaluate the effects of sequence variants and disease mutations on protein interactions and calculate the quantitative changes in binding affinity. The MutaBind method uses molecular mechanics force fields, statistical potentials and fast side-chain optimization algorithms. The MutaBind server maps mutations on a structural protein complex, calculates the associated changes in binding affinity, determines the deleterious effect of a mutation, estimates the confidence of this prediction and produces a mutant structural model for download. MutaBind can be applied to a large number of problems, including determination of potential driver mutations in cancer and other diseases, elucidation of the effects of sequence variants on protein fitness in evolution and protein design. MutaBind is available at http://www.ncbi.nlm.nih.gov/projects/mutabind/.
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ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkw374