Amino‐Acid Properties and Consequences of Substitutions

  title={Amino‐Acid Properties and Consequences of Substitutions},
  author={Matthew J. Betts and Robert B. Russell},
Since the earliest protein sequences and structures were determined, it has been clear that the positioning and properties of amino acids are key to understanding many biological processes (Pal et al., 2006). For example, the first-determined protein structure, haemoglobin, provided a molecular explanation for the genetic disease sickle cell anaemia. A single nucleotide mutation leads to a substitution of glutamate in normal individuals with valine in those who suffer the disease. The… 

Amino acid residue burial & co-evolution in proteins

A method is developed to investigate the relationship between specific co-substitution types and their propensity to occur at different physical separations in a protein structure.

Signature of a Primitive Genetic Code in Ancient Protein Lineages

This work performs a compositional analysis of ribosomal proteins and ATPase subunits in bacterial and archaeal lineages, using conserved positions that came and remained under purifying selection before and up to the most recent common ancestor to identify recent additions to the genetic code.

World-wide Sequence Variant and Non-synonymous Amino Acid Substitution Signature in SARS-COV-2 Structural Proteins

The amino acid substitution patterns and its impact on change in biochemical properties, thereby possible changes in protein structures are studied and the interesting fact that the substitution location is random in N protein, whereas the substitution sites in M protein is less varying and almost stable is revealed.

On Human Disease‐Causing Amino Acid Variants: Statistical Study of Sequence and Structural Patterns

Analysis of thermodynamics data reported in the literature indicated that disease‐causing variants tend to destabilize proteins and their interactions, which prompted us to investigate the effects of amino acid mutations on large databases of experimentally measured energy changes in unrelated proteins.

Combining sequence and structure information to model biological systems dynamics

There is a balance between physical adaptability and chemical specificity, and this balance underlies the selection of a relatively small set of versatile folds by proteins, according to a combined approach of sequence analyses and coarse-grained physics-based models.

DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage

This analysis indicates that indels in human protein coding regions are subject to distinct levels of selective pressure with regard to their structural impact on the amino acid sequence, as well as to general properties of the genes they are located in.

Predicting the structural effect upon single amino acid exchange

A machine-learning model was developed that successfully predicted structural effect induced by a single amino acid exchange and concluded that predicted functional impact alone sufficed to accurately predict whether a nsSNP leads to disease or not.

Context characterization of amino acid homorepeats using evolution, position, and order

This work presents evidence about the unevenly evolution of homorepeats, as well as the functional implications of their relative position in proteins, and establishes a basis for the study of other low complexity repeats.

Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent fitness landscapes

Comprehensive single-substitution mutational scanning of APH(3′)II, a Tn5 transposon-derived kinase that confers resistance to aminoglycoside antibiotics, in Escherichia coli under selection with each of six structurally diverse antibiotics at a range of inhibitory concentrations found that the resulting local fitness landscapes showed significant dependence on both antibiotic structure and concentration.



The structural basis of molecular adaptation.

Six studies are used to illustrate how phylogenies, site-directed mutagenesis, and a knowledge of protein structure combine to provide much deeper insights into the adaptive process than has hitherto been possible.

Mapping SNPs to protein sequence and structure data

The initial aim is to create a completely automatically maintained database of SAAPs mapped to individual residues in the Protein Data Bank (PDB) updated as new mutations or structures become available.

SNPs, protein structure, and disease

Ninety percent of the known disease‐causing missense mutations examined fit a model for assigning a mechanism of action of each mutation at the protein level, with the vast majority affecting protein stability, through a variety of energy related factors.

22 A Model of Evolutionary Change in Proteins

The body of data used in this study includes 1,572 changes of closely related proteins appearing in the Atlas volumes through Supplement 2 and the mutation data were accumulated from the phylo-genetic trees and from a few pairs of related sequences.

A mutation data matrix for transmembrane proteins

Detection of protein three-dimensional side-chain patterns: new examples of convergent evolution.

  • R. Russell
  • Computer Science
    Journal of molecular biology
  • 1998
A new method for detecting recurring three-dimensional side-chain patterns without any prior knowledge of function is presented, revealing several new examples of evolutionary convergence to common patterns of side-chains within different tertiary folds and in different orders along the sequence.

The classification of amino acid conservation.

Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins.

Characterization of single-nucleotide polymorphisms in coding regions of human genes

The cSNPs most likely to influence disease, those that alter the amino acid sequence of the encoded protein, are found at a lower rate and with lower allele frequencies than silent substitutions, likely reflects selection acting against deleterious alleles during human evolution.