Prokink: a protocol for numerical evaluation of helix distortions by proline

Abstract

Proline residues are known to perturb the structure of helices by introducing a kink between the segments preceding and following the proline residue. The distortion of the helical structure results from the avoided steric clash between the ring of the proline at position (i) and the backbone carbonyl at position (i - 4), as well as the elimination of helix backbone H-bonds for the carbonyls at positions (i - 3) and (i - 4). Both the departure from the ideal helical pattern and the reduction in H-bond stabilization contribute to the observed flexibility of a proline-containing alpha-helix. The special local flexibility of the proline kink can confer an important role on the proline-containing helix in the conformational changes related to the function of the protein. As a useful tool in determining and evaluating the role of proline-induced flexibility and distortions in protein function, we present here a protocol to quantify the geometry of the distortion introduced in helices by prolines both as a time-averaged value and for individual 'snapshots' along a molecular dynamics simulation.

Identification of Proline Residues in the Core Cytoplasmic and Transmembrane Regions of Multidrug Resistance Protein 1 (MRP1/ABCC1) Important for Transport Function, Substrate Specificity, and Nucleotide Interactions

“…Additionally or alternatively, Pro-kinks may contribute to a narrowing of the ends of a substrate translocation pathway and, in this way, contribute to the architecture of the "chamber" through which substrates are effluxed out of the cell. However, it has been established that the number of energetically favored conformations available to a kinked ␣-helix and its preferred bend angle can be altered by the residues surrounding the Pro (either within the same helix and/or in neighboring helices), and this alteration can be reflected in the functional properties of the mutants (37,51,52). Whether or not this is the case with any or all of the Pro-kink motifs in the MSD2 TM helices of MRP1 requires further investigation.…”

Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches

“…This program reorders the structures according to their root mean square deviation and groups the structures into families of similar conformers. The resulting 100 structures from CM were also analyzed using the program, ProKink (20). This program, which is embedded in the Simulaid Conversion program, 2 was used to calculate the face shift, wobble, and bend angles of each helix.…”

“…The wobble angle is the angle that defines the orientation of the post-proline helix in three-dimensional space, with respect to the pre-proline helix. The face shift measures the distortion that causes a twisting of the helix "face" in such a way that amino acids that used to be on the same side (face) of the helix are shifted and are on different sides of the helix as a result of the bend (20).…”

“…Because TMH6 is more kinked in the inactive state (R) and straightens in the activated state (R*), these two clusters are labeled R and R* in Table V ( 12). The ProKink program (20) was used to analyze each helix within each cluster in terms of bend angle, wobble angle, and face shift and to compute averages and standard deviations for each cluster.…”

Estudos conformacionais de seqüências hidrofóbicas de domínios de receptores acoplados a proteínas G (GPCR) e da proteína G. Um estudo de CD e espectroscopia de fluorescência

“…Visiers et aI. (25) propuseram que essas dobras podem ser I.Introdução Figura 5 -Estrutura cristalina da rodopsina resolvida por Palczewski et aI. (5).…”