Predicting the effect of a point mutation on a protein fold: the villin and advillin headpieces and their Pro62Ala mutants. J Mol Biol 2008 Jan 11;375(2):460-70
Date
11/21/2007Pubmed ID
18022635DOI
10.1016/j.jmb.2007.10.020Scopus ID
2-s2.0-36548999391 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
Homology modeling of unknown proteins is based on the assumption that highly similar sequences are likely to share the same fold. However, this does not provide any information on the stability of a given fold, which is ultimately determined by the subtle interplay of enthalpic and entropic contributions. Herein it is shown that ab initio atomistic simulations can be used to predict the effect of point mutations on the stability of a protein fold. The calculations indicate that the fold stabilities of two proteins of similar sequence and identical fold, the villin and advillin C-terminal headpiece fragments, are different and that the same P62A point mutation has a dramatic effect on the fold of villin but a minor one on that of advillin. These predictions were subsequently validated by NMR and CD experiments.
Author List
Piana S, Laio A, Marinelli F, Van Troys M, Bourry D, Ampe C, Martins JCAuthor
Fabrizio Marinelli PhD Associate Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlanineAmino Acid Motifs
Amino Acid Sequence
Circular Dichroism
Cluster Analysis
Computational Biology
Computer Simulation
Conserved Sequence
Hot Temperature
Humans
Hydrophobic and Hydrophilic Interactions
Kinetics
Microfilament Proteins
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Point Mutation
Protein Conformation
Protein Denaturation
Protein Folding
Protein Structure, Secondary
Sequence Homology, Amino Acid
Thermodynamics
