title: 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.
authors.affiliation: Computational Biophysics and Bioinformatics, Department of Physics and Astronomy, Clemson University, SC 29634, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Maria A
authors.initials: MA
authors.lastname: Miteva
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Emil
authors.initials: E
authors.lastname: Alexov
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D030541:Databases, Genetic; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics; D055550:Protein Stability; D013097:Spermine Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D013097:Spermine Synthase