Some useful ideas for multistate protein design: Effect of amino acid substitutions on the multistate proteins stability and the rate of protein structure formation

M A Majorina; T N Melnik; A S Glukhov; B S Melnik

doi:10.3389/fmolb.2022.983009

Some useful ideas for multistate protein design: Effect of amino acid substitutions on the multistate proteins stability and the rate of protein structure formation

Front Mol Biosci. 2022 Aug 26:9:983009. doi: 10.3389/fmolb.2022.983009. eCollection 2022.

Authors

M A Majorina¹, T N Melnik¹, A S Glukhov¹, B S Melnik^{1

2}

Affiliations

¹ Institute of Protein Research, Russian Academy of Sciences, Moscow, Russia.
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Abstract

The design of new protein variants is usually confined to slightly "fixing" an already existing protein, adapting it to certain conditions or to a new substrate. This is relatively easy to do if the fragment of the protein to be affected, such as the active site of the protein, is known. But what if you need to "fix" the stability of a protein or the rate of its native or intermediate state formation? Having studied a large number of protein mutant forms, we have established the effect of various amino acid substitutions on the energy landscape of the protein. As a result, we have revealed a number of patterns to help researchers identify amino acid residues that determine the folding rate and the stability of globular proteins states and design a mutant form of a protein with desired properties.

Keywords: amino acid substitutions; apomyoglobin; carbonic anhydrase; energy landscape of the protein; folding rate of multistste proteins; protein folding; stability of multistste proteins.