An efficient method to predict protein thermostability in alanine mutation

Ya Gao; Bo Wang; Shiyu Hu; Tong Zhu; John Z.H. Zhang

doi:10.1039/d2cp04236c

An efficient method to predict protein thermostability in alanine mutation

Ya Gao, Bo Wang, Shiyu Hu, Tong Zhu, John Z.H. Zhang

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔG) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔG_exp and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.

Original language	English (US)
Pages (from-to)	29629-29639
Number of pages	11
Journal	Physical Chemistry Chemical Physics
Volume	24
Issue number	48
DOIs	https://doi.org/10.1039/d2cp04236c
State	Published - Nov 16 2022

ASJC Scopus subject areas

General Physics and Astronomy
Physical and Theoretical Chemistry

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10.1039/d2cp04236c

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title = "An efficient method to predict protein thermostability in alanine mutation",

abstract = "The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔG) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔGexp and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.",

author = "Ya Gao and Bo Wang and Shiyu Hu and Tong Zhu and Zhang, {John Z.H.}",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 21933010, 22250710136, and 62072296), NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the Supercomputer Center of East China Normal University (ECNU Public Platform for Innovation 001) for providing us computational time. Publisher Copyright: {\textcopyright} 2022 The Royal Society of Chemistry.",

year = "2022",

month = nov,

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doi = "10.1039/d2cp04236c",

language = "English (US)",

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publisher = "Royal Society of Chemistry",

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T1 - An efficient method to predict protein thermostability in alanine mutation

AU - Gao, Ya

AU - Wang, Bo

AU - Hu, Shiyu

AU - Zhu, Tong

AU - Zhang, John Z.H.

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 21933010, 22250710136, and 62072296), NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the Supercomputer Center of East China Normal University (ECNU Public Platform for Innovation 001) for providing us computational time. Publisher Copyright: © 2022 The Royal Society of Chemistry.

PY - 2022/11/16

Y1 - 2022/11/16

N2 - The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔG) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔGexp and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.

AB - The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔG) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔGexp and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.

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JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

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An efficient method to predict protein thermostability in alanine mutation

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