کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
444615 693016 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparison of computational approaches for predicting the effects of missense mutations on p53 function
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Comparison of computational approaches for predicting the effects of missense mutations on p53 function
چکیده انگلیسی

We applied our recently developed kinetic computational mutagenesis (KCM) approach [L.T. Chong, W.C. Swope, J.W. Pitera, V.S. Pande, Kinetic computational alanine scanning: application to p53 oligomerization, J. Mol. Biol. 357 (3) (2006) 1039–1049] along with the MM-GBSA approach [J. Srinivasan, T.E. Cheatham 3rd, P. Cieplak, P.A. Kollman, D.A. Case, Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate-DNA helices, J. Am. Chem. Soc. 120 (37) (1998) 9401–9409; P.A. Kollman, I. Massova, C.M. Reyes, B. Kuhn, S. Huo, L.T. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J. Srinivasan, D.A. Case, T.E. Cheatham 3rd., Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models, Acc. Chem. Res. 33 (12) (2000) 889–897] to evaluate the effects of all possible missense mutations on dimerization of the oligomerization domain (residues 326–355) of tumor suppressor p53. The true positive and true negative rates for KCM are comparable (within 5%) to those of MM-GBSA, although MM-GBSA is much less computationally intensive when it is applied to a single energy-minimized configuration per mutant dimer. The potential advantage of KCM is that it can be used to directly examine the kinetic effects of mutations.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 27, Issue 8, June–July 2009, Pages 978–982
نویسندگان
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