In the protein dimer remains unaltered, but its dynamics in a native membrane environment is greater described in bicelles.471 Among the host of simulations of peptides in DPC micelles, quite a few of them combined synergistically MD and NMR spectroscopy to render an enhanced picture with the interactions at play.349,470,472-474,476-478 In their simulations, Abel et al. examine the spatial arrangement of 4 membrane-spanning domains of an ABC transporter in DPC and DDM micelles, and report that these peptide chains migrate to the interfacial region, having a deeper penetration inside the DDM detergents in addition to a lesser tendency to unfold.475 Turning toReviewan implicit-solvent Misoprostol Epigenetics description, Versace and Lazaridis examined a variety of interfacial peptides and -barrel MPs in both DPC and SDS micelles, and noted little conformational deformation with respect for the reference, experimental structures.479 In their investigation of the N-terminal region of hemagglutinin in DPC micelles and within a DMPC bilayer, Victor et al. showed that this fusion peptide remains fully structured in the detergent medium, and adopts a membrane-spanning conformation inside the bilayer, distorting locally the latter.480 Im and co-workers have developed a hassle-free tool for the building of detergent micelles hosting proteins and peptides, and have applied it towards the systematic study of a voltage-dependent potassium channel along with the papiliocin peptide, showing an asymptotic limit from the protein-detergent interactions using the variety of both DPC and DHPC detergent molecules.481 Molecular simulations are a versatile tool for studying the structure, dynamics, and ligand/lipid-interactions of MPs. Such simulations can furthermore not merely be employed to investigate MPs close to their equilibrium conformation, but additionally address the physiological relevance of structures obtained in non-native environments, and rationalize the interactions of detergents with MPs, as highlighted with numerous case research presented in section 4.1.6. CONCLUSIONS MPs are a challenge in the standpoint of sample preparation and handling also as for biophysical and structural strategies. Their size, heterogeneity, and intrinsic dynamics represent extreme technical hurdles for structural and functional studies. The physiological relevance of MP structures has constantly been a matter of debate, in the theoretical at the same time as the experimental level. Every single approach has its particular needs and may introduce specific artifacts. Crystallization selects a single conformation on the protein, the relevance of which has to be asserted by further experiments. Not all conformations existing inside a membrane may very well be prone to crystallization, creating it hard to decipher mechanistic specifics from a single frozen conformation. NMR spectroscopy, in its solution- and solid-state variants, is hence complementary to crystallography, mainly because the technique can characterize proteins even when they coexist in multiple conformations, thereby giving access to systems that happen to be not amenable to crystallography. However, as such measurements are virtually generally performed in non-native environments, the central question should be to which extent the ensemble of conformations existing inside a offered membranemimicking environment reflects those present in membranes. Within this Review, we have highlighted the effects of alkyl phosphocholines, and particularly DPC, on MP structure, interactions, dynamics, and function. The fact that DPC is by far one of the most widel.