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Analyzing Effects of Naturally Occurring Missense Mutations

Analyzing effects of naturally occurring missense mutations
Authors: Zhang, Zhe; Miteva, Maria A; Wang, Lin; Alexov, Emil;

Analyzing Effects of Naturally Occurring Missense Mutations

Abstract

Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well.

Keywords

Models, Molecular, Protein Folding, Biochemistry, molecular biology, Spermine Synthase, Mutation, Missense, Review Article, Molecular Dynamics Simulation, Polymorphism, Single Nucleotide, Problems related to evolution, Artificial Intelligence, Databases, Genetic, Humans, Computer Simulation, Protein Interaction Domains and Motifs, Computational methods for problems pertaining to biology, Biological and Chemical Physics, Binding Sites, Models, Genetic, Protein Stability, Physics, Kinetics, Mutant Proteins, Protein Multimerization, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
123
Top 1%
Top 10%
Top 10%
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gold