ArticleJournal of the American Chemical Society2011
Computational design of thermostabilizing D-amino acid substitutions.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 45 citations in OpenAlex.
- Rational design of the genetic code expansion toolkit forFrontiers in genetics · 2023Article
- Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes.Nanoscale advances · 2022Article
- D-Amino acid substituted peptides as potential alternatives of homochiral L-configurations.Amino acids · 2021Article
- Analysis of folded structure and folding thermodynamics in heterogeneous-backbone proteomimetics.Methods in enzymology · 2021Review
- Application of a Distance-Dependent Sigmoidal Dielectric Constant to the REMC/SAAP3D Simulations of Chignolin, Trp-Cage, and the G10q Mutant.The protein journal · 2020Article
- Computational study on the polymerization reaction of d-aminopeptidase for the synthesis of d-peptides.RSC advances · 2020Article
- Adevonin, a novel synthetic antimicrobial peptide designed from the Adenanthera pavonina trypsin inhibitor (ApTI) sequence.Pathogens and global health · 2018Article
- Molecular dynamics-derived rotamer libraries for d-amino acids within homochiral and heterochiral polypeptides.Protein engineering, design & selection : PEDS · 2018Article
- Fast and Effective Ion Mobility-Mass Spectrometry Separation of d-Amino-Acid-Containing Peptides.Analytical chemistry · 2017Article
- Insights from molecular dynamics simulations for computational protein design.Molecular systems design & engineering · 2017Article
- Experimental and Computational Analysis of Protein Stabilization by Gly-to-d-Ala Substitution: A Convolution of Native State and Unfolded State Effects.Journal of the American Chemical Society · 2016Article
- Article
- Empirical estimation of local dielectric constants: Toward atomistic design of collagen mimetic peptides.Biopolymers · 2015Article
- D-amino acids modulate the cellular response of enzymatic-instructed supramolecular nanofibers of small peptides.Biomacromolecules · 2014Article
- Folding Thermodynamics of Protein-Like Oligomers with Heterogeneous Backbones.Chemical science · 2014Article
- Circular Permutation of the Trp-cage: Fold Rescue upon Addition of a Hydrophobic Staple.RSC advances · 2013Article
- Using D-Amino Acids to Delineate the Mechanism of Protein Folding: Application to Trp-cage.Chemical physics · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Judicious incorporation of D-amino acids in engineered proteins confers many advantages such as preventing degradation by endogenous proteases and promoting novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing D-amino acid mutations. Substituting a key glycine in the Trp-cage miniprotein with D-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces both at the α-helix C-terminus and throughout the protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.