ENVIRON: a software package to compare protein three-dimensional structures with homologous sequences using local...

Area of Science:

• Structural bioinformatics
• Computational biology
• Protein science

Background:

• Protein structure and function are intricately linked to residue interactions.
• Homologous sequences can provide insights into conserved structural and functional elements.
• Understanding local residue environments is crucial for predicting protein behavior.

Purpose of the Study:

• To develop a method for comparing local residue clusters between 3D protein structures and homologous sequences.
• To identify conserved local features and environmental similarities in proteins.
• To provide a tool for investigating protein function and guiding mutagenesis experiments.

Main Methods:

• Defining the local environment of a residue as contacting amino acids in a 3D structure.
• Utilizing multiple sequence alignment to identify equivalent residues in homologous proteins.
• Comparing template protein structure environments with inferred environments from aligned sequences.

Main Results:

• The method allows detection of conserved local features like hydrogen bonding and complementary residue substitutions.
• A global measure of environmental similarity was defined to identify constrained amino acid clusters.
• The approach successfully highlights conserved patterns in local protein environments.

Conclusions:

• The developed method effectively compares local residue environments across homologous proteins.
• This approach aids in understanding protein function and evolutionary constraints on residue clusters.
• It offers a valuable tool for suggesting beneficial amino acid substitutions in site-directed mutagenesis.