Predicting the Effect of a Point Mutation on a Protein Fold: The Villin and Advillin Headpieces and Their Pro62Ala Mutants Export

@article{citeulike:1786166, abstract = {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 = {Piana, Stefano and Laio, Alessandro and Marinelli, Fabrizio and Van Troys, Marleen and Bourry, David and Ampe, Christophe and Martins, Jos\'{e} C.}, citeulike-article-id = {1786166}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jmb.2007.10.020}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0022283607013423}, citeulike-linkout-2 = {http://www.sciencedirect.com/science/article/B6WK7-4PWKSYT-5/2/090c0a1f1ddbe682296a6caa65ceab11}, day = {11}, doi = {10.1016/j.jmb.2007.10.020}, issn = {00222836}, journal = {Journal of Molecular Biology}, keywords = {folding, metadynamics, molecular\_dynamics, nmr}, month = {January}, number = {2}, pages = {460--470}, posted-at = {2009-01-15 10:39:32}, priority = {2}, title = {Predicting the Effect of a Point Mutation on a Protein Fold: The Villin and Advillin Headpieces and Their Pro62Ala Mutants}, url = {http://dx.doi.org/10.1016/j.jmb.2007.10.020}, volume = {375}, year = {2008} }

TY - JOUR ID - citeulike:1786166 L3 - citeulike-article-id:1786166 N2 - 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. IS - 2 JF - Journal of Molecular Biology SN - 00222836 EP - 470 TI - Predicting the Effect of a Point Mutation on a Protein Fold: The Villin and Advillin Headpieces and Their Pro62Ala Mutants VL - 375 SP - 460 KW - folding KW - metadynamics KW - molecular_dynamics KW - nmr AU - Piana, Stefano AU - Laio, Alessandro AU - Marinelli, Fabrizio AU - Van Troys, Marleen AU - Bourry, David AU - Ampe, Christophe AU - Martins, José PY - 2008/01/11/ UR - http://dx.doi.org/10.1016/j.jmb.2007.10.020 ER -