title: Role of Molecular Flexibility and Colloidal Descriptions of Proteins in Crowded Environments from Small-Angle Scattering.
abstract: Small-angle scattering is a powerful technique to study molecular conformation and interactions of proteins in solution and in amorphous solids. We have investigated the role of multiple protein configurations in the interaction parameters derived from small-angle scattering for proteins in concentrated solutions. In order to account for the wide configurational space sampled by proteins, we generate ensembles of atomistic structures for lysozyme and monoclonal antibodies, representing globular and flexible proteins, respectively. While recent work has argued that a colloidal approach is inadequate to model proteins, because of the large configurational space that they sample in solution, we find a range of length scales where colloidal models can be used to describe solution scattering data while simultaneously accounting for structural flexibility. We provide insights to determine the length scales where isotropic colloidal models can be used, and find smoothly varying sets of interaction parameters that encompass ensembles of structures. This approach may play an important role in the definition of long-range interactions in coarse-grained models of flexible proteins with experimental scattering constraints. Additionally, we apply the decoupling approximation to ensembles of lysozyme structures with atomistic detail and observe remarkably different results when using geometric solids, such as ellipsoids. The insights from this study provide guidelines for the analysis of small-angle scattering profiles of proteins in crowded environments.
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology , 100 Bureau Drive, Mail Stop 6102, Gaithersburg, Maryland 20899, United States.|Institute for Bioscience and Biotechnology Research , 9600 Gudelsky Drive, Rockville, Maryland 20850, United States.
authors.forename: Maria Monica
authors.initials: MM
authors.lastname: Castellanos
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology , 100 Bureau Drive, Mail Stop 6102, Gaithersburg, Maryland 20899, United States.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Clark
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology , 100 Bureau Drive, Mail Stop 6102, Gaithersburg, Maryland 20899, United States.
authors.forename: Max C
authors.initials: MC
authors.lastname: Watson
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology , 100 Bureau Drive, Mail Stop 6102, Gaithersburg, Maryland 20899, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Krueger
authors.affiliation: Department of Drug Product Development, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Arnold
authors.initials: A
authors.lastname: McAuley
authors.affiliation: NIST Center for Neutron Research, National Institute of Standards and Technology , 100 Bureau Drive, Mail Stop 6102, Gaithersburg, Maryland 20899, United States.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Curtis
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D003102:Colloids; D008027:Light; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry*; D011487:Protein Conformation; D053838:Scattering, Small Angle; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D003102:Colloids; D009113:Muramidase