Modeling protein recognition of carbohydrates.
We have a limited understanding of the details of molecular recognition of carbohydrates by proteins, which is critical to a multitude of biological processes. Furthermore, carbohydrate-modifying proteins such as glycosyl hydrolases and phosphorylases are of growing importance as potential drug targets. Interactions between proteins and carbohydrates have complex thermodynamics, and in general the specific positioning of only a few hydroxyl groups determines their binding affinities. A thorough understanding of both carbohydrate and protein structures is thus essential to predict these interactions. An atomic-level view of carbohydrate recognition through structures of carbohydrate-active enzymes complexed with transition-state inhibitors reveals some of the distinctive molecular features unique to protein-carbohydrate complexes. However, the inherent flexibility of carbohydrates and their often water-mediated hydrogen bonding to proteins makes simulation of their complexes difficult. Nonetheless, recent developments such as the parameterization of specific force fields and docking scoring functions have greatly improved our ability to predict protein-carbohydrate interactions. We review protein-carbohydrate complexes having defined molecular requirements for specific carbohydrate recognition by proteins, providing an overview of the different computational techniques available to model them.
Department of Chemical Engineering, Iowa State University, Ames, Iowa 50011-2230, USA.
Alain
A
Laederach
Peter J
PJ
Reilly
D020909:Acarbose / Q000737:chemistry / Q000378:metabolism; D000936:Antigen-Antibody Complex; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D003208:Concanavalin A / Q000737:chemistry; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D005087:Glucan 1,4-alpha-Glucosidase / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013816:Thermodynamics; D014312:Trisaccharides / Q000737:chemistry
D000936:Antigen-Antibody Complex; D002241:Carbohydrates; D004798:Enzymes; D014312:Trisaccharides; D003208:Concanavalin A; D005087:Glucan 1,4-alpha-Glucosidase; D020909:Acarbose