Theoretical and Computational Studies of Peptides and Receptors of the Insulin Family

Membranes

Harish Vashisth¹ 

[1] Department of Chemical Engineering, University of New Hampshire, 33 Academic Way, Durham, NH 03824, USA; E-Mai

关键词: insulin;    insulin-like growth factors;    receptor tyrosine kinases;    computer simulations;    docking;    enhanced sampling;    signal transduction;   

DOI  :  10.3390/membranes5010048

来源: mdpi

【 摘 要 】

Synergistic interactions among peptides and receptors of the insulin family are required for glucose homeostasis, normal cellular growth and development, proliferation, differentiation and other metabolic processes. The peptides of the insulin family are disulfide-linked single or dual-chain proteins, while receptors are ligand-activated transmembrane glycoproteins of the receptor tyrosine kinase (RTK) superfamily. Binding of ligands to the extracellular domains of receptors is known to initiate signaling via activation of intracellular kinase domains. While the structure of insulin has been known since 1969, recent decades have seen remarkable progress on the structural biology of apo and liganded receptor fragments. Here, we review how this useful structural information (on ligands and receptors) has enabled large-scale atomically-resolved simulations to elucidate the conformational dynamics of these biomolecules. Particularly, applications of molecular dynamics (MD) and Monte Carlo (MC) simulation methods are discussed in various contexts, including studies of isolated ligands, apo-receptors, ligand/receptor complexes and intracellular kinase domains. The review concludes with a brief overview and future outlook for modeling and computational studies in this family of proteins.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland