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

Abstract:

: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/.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Li M,Simonetti FL,Goncearenco A,Panchenko AR

doi

10.1093/nar/gkw374

subject

Has Abstract

pub_date

2016-07-08 00:00:00

pages

W494-501

issue

W1

eissn

0305-1048

issn

1362-4962

pii

gkw374

journal_volume

44

pub_type

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