Document Type

Article

Publication Date

11-2013

Publication Title

Journal of Molecular Biology

Volume

425

Issue

21

Publisher

Elsevier

Abstract

Genetic variations resulting in a change of amino acid sequence can have a dramatic effect on stability, hydrogen bond network, conformational dynamics, activity and many other physiologically important properties of proteins. The substitutions of only one residue in a protein sequence, so-called missense mutations, can be related to many pathological conditions, and may influence susceptibility to disease and drug treatment. The plausible effects of missense mutations range from affecting the macromolecular stability to perturbing macromolecular interactions and cellular localization. Here we review the individual cases and genome-wide studies which illustrate the association between missense mutations and diseases. In addition we emphasize that the molecular mechanisms of effects of mutations should be revealed in order to understand the disease origin. Finally we report the current state-of-the-art methodologies which predict the effects of mutations on protein stability, the hydrogen bond network, pH-dependence, conformational dynamics and protein function.

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This manuscript has been published in the Journal of Molecular Biology. Please find the published version here (note that a subscription is necessary to access this version):

http://www.sciencedirect.com/science/article/pii/S0022283613004464

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