title: Conformational sampling of peptides in the presence of protein crowders from AA/CG-multiscale simulations.
abstract: Macromolecular crowding is recognized as an important factor influencing folding and conformational dynamics of proteins and nucleic acids. Previous views of crowding have focused on the mostly entropic volume exclusion effect of crowding, but recent studies are indicating the importance of enthalpic effects, in particular, changes in electrostatic interactions due to crowding. Here, temperature replica exchange molecular dynamics simulations of trp-cage and melittin in the presence of explicit protein crowders are presented to further examine the effect of protein crowders on peptide dynamics. The simulations involve a three-component multiscale modeling scheme where the peptides are represented at an atomistic level, the crowder proteins at a coarse-grained level, and the surrounding aqueous solvent as implicit solvent. This scheme optimally balances a physically realistic description for the peptide with computational efficiency. The multiscale simulations were compared with simulations of the same peptides in different dielectric environments with dielectric constants ranging from 5 to 80. It is found that the sampling in the presence of the crowders resembles sampling with reduced dielectric constants between 10 and 40. Furthermore, diverse conformational ensembles are generated in the presence of crowders including partially unfolded states for trp-cage. These findings emphasize the importance of enthalpic interactions over volume exclusion effects in describing the effects of cellular crowding.
authors.affiliation: Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Predeus
authors.forename: Seref
authors.initials: S
authors.lastname: Gul
authors.forename: Srinivasa M
authors.initials: SM
authors.lastname: Gopal
authors.forename: Michael
authors.initials: M
authors.lastname: Feig
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D001516:Bees / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013291:Streptococcus / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D010455:Peptides; D011506:Proteins; C043431:M antigen, Brucella melitensis