کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1994574 1064801 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular modelling methods for prediction of sequence-selectivity in DNA recognition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Molecular modelling methods for prediction of sequence-selectivity in DNA recognition
چکیده انگلیسی

We describe how one can apply molecular modelling methods, based on the molecular mechanics/generalised Born (MM/GB) approach, to the prediction of the relative affinity of DNA minor groove binding ligands for different DNA sequences. We discuss the theoretical background to the technique, some variations in the methodology that can be employed, and illustrate its application through a case study: analysis of the energetics of binding of Hoechst 33258 to the minor groove of various A/T-rich DNA duplexes. We show how the underpinning molecular dynamics (MD) simulations can be set up, how they can be analysed for satisfactory behaviour, and various approaches to extracting thermodynamics of drug binding from them. We find that while certain elaborations to the basic MM/GB method can improve the agreement with experimental data (e.g., calculating the DNA perturbation energy), others have to be analysed with more caution (e.g., calculating configurational entropy changes). Overall, these methodologies can rank the affinity of a ligand for the minor groove of different DNA sequences fairly well, but the calculation of absolute binding affinities is not very reliable.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 42, Issue 2, June 2007, Pages 196–203
نویسندگان
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