کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1959149 1057928 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular Dynamics Simulation of WSK-3, a Computationally Designed, Water-Soluble Variant of the Integral Membrane Protein KcsA
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Molecular Dynamics Simulation of WSK-3, a Computationally Designed, Water-Soluble Variant of the Integral Membrane Protein KcsA
چکیده انگلیسی

Poor solubility and low expression levels often make membrane proteins difficult to study. An alternative to the use of detergents to solubilize these aggregation-prone proteins is the partial redesign of the sequence so as to confer water solubility. Recently, computationally assisted membrane protein solubilization (CAMPS) has been reported, where exposed hydrophobic residues on a protein’s surface are computationally redesigned. Herein, the structure and fluctuations of a designed, water-soluble variant of KcsA (WSK-3) were studied using molecular dynamics simulations. The root mean square deviation of the protein from its starting structure, where the backbone coordinates are those of KcsA, was 1.8 Å. The structure of salt bridges involved in structural specificity and solubility were examined. The preferred configuration of ions and water in the selectivity filter of WSK-3 was consistent with the reported preferences for KcsA. The structure of the selectivity filter was maintained, which is consistent with WSK-3 having an affinity for agitoxin2 comparable to that of wild-type KcsA. In contrast to KcsA, the central cavity’s side chains were observed to reorient, allowing water diffusion through the side of the cavity wall. These simulations provide an atomistic analysis of the CAMPS strategy and its implications for further investigations of membrane proteins.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 90, Issue 4, 15 February 2006, Pages 1156–1163
نویسندگان
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