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Equilibrium transitions between side‐chain conformations in leucine and isoleucine

Equilibrium transitions between side‐chain conformations in leucine and isoleucine ABSTRACT Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic probabilities for amino acids to adopt particular side‐chain conformations. Surprisingly, this question has remained unsettled for many years, in part because of inconsistent results from different experimental approaches. To explicitly determine the relative populations of different side‐chain dihedral angles, we performed all‐atom hard‐sphere Langevin Dynamics simulations of leucine (Leu) and isoleucine (Ile) dipeptide mimetics with stereo‐chemical constraints and repulsive‐only steric interactions between non‐bonded atoms. We determine the relative populations of the different χ1 and χ2 dihedral angle combinations as a function of the backbone dihedral angles ϕ and ψ. We also propose, and test, a mechanism for inter‐conversion between the different side‐chain conformations. Specifically, we discover that some of the transitions between side‐chain dihedral angle combinations are very frequent, whereas others are orders of magnitude less frequent, because they require rare coordinated motions to avoid steric clashes. For example, to transition between different values of χ2, the Leu side‐chain bond angles κ1 and κ2 must increase, whereas to transition in χ1, the Ile bond angles λ1 and λ2 must increase. These results emphasize the importance of computational approaches in stimulating further experimental studies of the conformations of side‐chains in proteins. Moreover, our studies emphasize the power of simple steric models to inform our understanding of protein structure, dynamics, and design. Proteins 2015; 83:1488–1499. © 2015 Wiley Periodicals, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Proteins: Structure Function and Bioinformatics Wiley

Equilibrium transitions between side‐chain conformations in leucine and isoleucine

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References (52)

Publisher
Wiley
Copyright
© 2015 Wiley Periodicals, Inc.
ISSN
0887-3585
eISSN
1097-0134
DOI
10.1002/prot.24837
pmid
26018846
Publisher site
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Abstract

ABSTRACT Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic probabilities for amino acids to adopt particular side‐chain conformations. Surprisingly, this question has remained unsettled for many years, in part because of inconsistent results from different experimental approaches. To explicitly determine the relative populations of different side‐chain dihedral angles, we performed all‐atom hard‐sphere Langevin Dynamics simulations of leucine (Leu) and isoleucine (Ile) dipeptide mimetics with stereo‐chemical constraints and repulsive‐only steric interactions between non‐bonded atoms. We determine the relative populations of the different χ1 and χ2 dihedral angle combinations as a function of the backbone dihedral angles ϕ and ψ. We also propose, and test, a mechanism for inter‐conversion between the different side‐chain conformations. Specifically, we discover that some of the transitions between side‐chain dihedral angle combinations are very frequent, whereas others are orders of magnitude less frequent, because they require rare coordinated motions to avoid steric clashes. For example, to transition between different values of χ2, the Leu side‐chain bond angles κ1 and κ2 must increase, whereas to transition in χ1, the Ile bond angles λ1 and λ2 must increase. These results emphasize the importance of computational approaches in stimulating further experimental studies of the conformations of side‐chains in proteins. Moreover, our studies emphasize the power of simple steric models to inform our understanding of protein structure, dynamics, and design. Proteins 2015; 83:1488–1499. © 2015 Wiley Periodicals, Inc.

Journal

Proteins: Structure Function and Bioinformatics – Wiley

Published: Aug 1, 2015

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