The Empirical Valence Bond As an Effective Strategy for Computer-aided Enzyme Design

Overview

Journal Biotechnol J

Specialty Biotechnology

Date 2009 Feb 21

PMID 19229886

Citations 6

Authors

Alexandra Vardi-Kilshtain

Maite Roca

Arieh Warshel

Affiliations

Soon will be listed here.

Abstract

The ability of the empirical valence bond (EVB) to be used in screening active site residues in enzyme design is explored in a preliminary way. This validation is done by comparing the ability of this approach to evaluate the catalytic contributions of various residues in chorismate mutase. It is demonstrated that the EVB model can serve as an accurate tool in the final stages of computer-aided enzyme design (CAED). The ability of the model to predict quantitatively the catalytic power of enzymes should augment the capacity of current approaches for enzyme design.

Citing Articles

Engineering Dehalogenase Enzymes Using Variational Autoencoder-Generated Latent Spaces and Microfluidics.

Kohout P, Vasina M, Majerova M, Novakova V, Damborsky J, Bednar D JACS Au. 2025; 5(2):838-850.

PMID: 40017771 PMC: 11862945. DOI: 10.1021/jacsau.4c01101.

Exploring the Development of Ground-State Destabilization and Transition-State Stabilization in Two Directed Evolution Paths of Kemp Eliminases.

Jindal G, Ramachandran B, Bora R, Warshel A ACS Catal. 2017; 7(5):3301-3305.

PMID: 29082065 PMC: 5658032. DOI: 10.1021/acscatal.7b00171.

On the challenge of exploring the evolutionary trajectory from phosphotriesterase to arylesterase using computer simulations.

Bora R, Mills M, Frushicheva M, Warshel A J Phys Chem B. 2015; 119(8):3434-45.

PMID: 25620270 PMC: 11343073. DOI: 10.1021/jp5124025.

Computer aided enzyme design and catalytic concepts.

Frushicheva M, Mills M, Schopf P, Singh M, Prasad R, Warshel A Curr Opin Chem Biol. 2014; 21:56-62.

PMID: 24814389 PMC: 4149935. DOI: 10.1016/j.cbpa.2014.03.022.

Modeling catalytic promiscuity in the alkaline phosphatase superfamily.

Duarte F, Amrein B, Kamerlin S Phys Chem Chem Phys. 2013; 15(27):11160-77.

PMID: 23728154 PMC: 3693508. DOI: 10.1039/c3cp51179k.

References

Liu H, Warshel A . The catalytic effect of dihydrofolate reductase and its mutants is determined by reorganization energies. Biochemistry. 2007; 46(20):6011-25. DOI: 10.1021/bi700201w. View

Seelig B, Szostak J . Selection and evolution of enzymes from a partially randomized non-catalytic scaffold. Nature. 2007; 448(7155):828-31. PMC: 4476047. DOI: 10.1038/nature06032. View

Lippow S, Tidor B . Progress in computational protein design. Curr Opin Biotechnol. 2007; 18(4):305-11. PMC: 3495006. DOI: 10.1016/j.copbio.2007.04.009. View

Strajbl M, Shurki A, Kato M, Warshel A . Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization. J Am Chem Soc. 2003; 125(34):10228-37. DOI: 10.1021/ja0356481. View

Bjelic S, Aqvist J . Catalysis and linear free energy relationships in aspartic proteases. Biochemistry. 2006; 45(25):7709-23. DOI: 10.1021/bi060131y. View

Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View

Rao S, Singh U, Bash P, Kollman P . Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin. Nature. 1987; 328(6130):551-4. DOI: 10.1038/328551a0. View

Florian J, Goodman M, Warshel A . Computer simulations of protein functions: searching for the molecular origin of the replication fidelity of DNA polymerases. Proc Natl Acad Sci U S A. 2005; 102(19):6819-24. PMC: 1100748. DOI: 10.1073/pnas.0408173102. View

Marti S, Andres J, Moliner V, Silla E, Tunon I, Bertran J . Predicting an improvement of secondary catalytic activity of promiscuous isochorismate pyruvate lyase by computational design. J Am Chem Soc. 2008; 130(10):2894-5. DOI: 10.1021/ja078334c. View

10.

Varadarajan N, Gam J, Olsen M, Georgiou G, Iverson B . Engineering of protease variants exhibiting high catalytic activity and exquisite substrate selectivity. Proc Natl Acad Sci U S A. 2005; 102(19):6855-60. PMC: 1100772. DOI: 10.1073/pnas.0500063102. View

11.

Hansson T, Nordlund P, Aqvist J . Energetics of nucleophile activation in a protein tyrosine phosphatase. J Mol Biol. 1997; 265(2):118-27. DOI: 10.1006/jmbi.1996.0716. View

12.

Roca M, Messer B, Hilvert D, Warshel A . On the relationship between folding and chemical landscapes in enzyme catalysis. Proc Natl Acad Sci U S A. 2008; 105(37):13877-82. PMC: 2544547. DOI: 10.1073/pnas.0803405105. View

13.

Warshel A, Sharma P, Kato M, Xiang Y, Liu H, Olsson M . Electrostatic basis for enzyme catalysis. Chem Rev. 2006; 106(8):3210-35. DOI: 10.1021/cr0503106. View

14.

Hwang J, Warshel A . Semiquantitative calculations of catalytic free energies in genetically modified enzymes. Biochemistry. 1987; 26(10):2669-73. DOI: 10.1021/bi00384a003. View

15.

Toscano M, Woycechowsky K, Hilvert D . Minimalist active-site redesign: teaching old enzymes new tricks. Angew Chem Int Ed Engl. 2007; 46(18):3212-36. DOI: 10.1002/anie.200604205. View

16.

Vamvaca K, Vogeli B, Kast P, Pervushin K, Hilvert D . An enzymatic molten globule: efficient coupling of folding and catalysis. Proc Natl Acad Sci U S A. 2004; 101(35):12860-4. PMC: 516485. DOI: 10.1073/pnas.0404109101. View

17.

Warshel A, Sussman F . Toward computer-aided site-directed mutagenesis of enzymes. Proc Natl Acad Sci U S A. 1986; 83(11):3806-10. PMC: 323612. DOI: 10.1073/pnas.83.11.3806. View

18.

Chook Y, Gray J, Ke H, Lipscomb W . The monofunctional chorismate mutase from Bacillus subtilis. Structure determination of chorismate mutase and its complexes with a transition state analog and prephenate, and implications for the mechanism of the enzymatic reaction. J Mol Biol. 1994; 240(5):476-500. DOI: 10.1006/jmbi.1994.1462. View

19.

Kaplan J, Degrado W . De novo design of catalytic proteins. Proc Natl Acad Sci U S A. 2004; 101(32):11566-70. PMC: 511021. DOI: 10.1073/pnas.0404387101. View

20.

Martinek V, Bren U, Goodman M, Warshel A, Florian J . DNA polymerase beta catalytic efficiency mirrors the Asn279-dCTP H-bonding strength. FEBS Lett. 2007; 581(4):775-80. PMC: 2001272. DOI: 10.1016/j.febslet.2007.01.042. View