Conformational Ensemble Generation via Constraint-based Rigid-body Dynamics Guided by the Elastic Network Model

protein structure;normal mode analysis;rigidity;rigid-body dynamics;ligand binding;Computer Science

Borowski, Krzysztof

University of Waterloo

关键词: protein structure;    normal mode analysis;    rigidity;    rigid-body dynamics;    ligand binding;    Computer Science;   

Others  :  https://uwspace.uwaterloo.ca/bitstream/10012/6162/1/Borowski_Krzysztof.pdf

瑞士|英语

来源: UWSPACE Waterloo Institutional Repository

【 摘 要 】

Conformational selection is the idea that proteins traverse positions on theconformational space represented by their potential energy landscape, and in particular positions considered as local energy minima. Conformational selection a useful concept in ligand binding studies and in exploring thebehavior of protein structures within that energy landscape. Often, research that explores protein function requires the generation of conformational ensembles, or collections of protein conformations from a single structure. We describe a method of conformational ensemble generation that uses joint-constrained rigid-body dynamics (an approach that allows for explicit consideration of rigidity) and the elastic network model (providing structurally derived directional guides for the rigid-body model). We test our model on a selection of unbound proteins and examine the structural validity of the resulting ensembles, as well as the ability of such an approach to generate conformations with structural overlaps close to the ligand-bound versions of the proteins.