Related Experiment Video
Updated: Feb 24, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Exact correspondence between walk in nucleotide and protein sequence spaces
Dmitry N Ivankov1,2,3
1Laboratory of Evolutionary Genomics, Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain.
This study introduces an algorithm to calculate accessible protein sequences from gene mutations. The method reveals a significantly larger number of reachable protein sequences than previously estimated, aiding evolutionary studies.
Area of Science:
- Evolutionary biology
- Bioinformatics
- Computational biology
Background:
- Genes evolve through nucleotide sequence changes, altering protein sequences.
- The precise mapping between nucleotide and protein sequence spaces remains incompletely understood.
- Quantifying reachable protein sequences after a set number of mutations is an open question.
Purpose of the Study:
- To develop an algorithm for calculating the volume of protein sequence space accessible from a given protein sequence.
- To determine the number of protein sequences reachable with a specific number of nucleotide substitutions.
Main Methods:
- Algorithm development utilizing dynamic programming.
- Calculation of accessible protein sequence space volume.
- Application to green fluorescence protein (GFP) as a case study.
Main Results:
- The algorithm efficiently calculates accessible protein sequence space volume on a desktop computer.
- For GFP, the algorithm estimated four times more reachable sequences than prior estimations.
- Despite the increase, previous estimates remain valid as order-of-magnitude approximations.
Conclusions:
- The developed algorithm provides a precise method for quantifying evolutionary trajectories in sequence space.
- This tool has practical applications in understanding protein evolution and sequence space exploration.
- The findings refine our understanding of the relationship between genetic mutations and protein diversity.
Related Concept Videos
From DNA to Protein
DNA as a Genetic Template
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Evolutionary Relationships through Genome Comparisons
Conservation of Protein Domains

