Sequence codes for extended conformation: A neighbor-dependent sequence analysis of loops in proteins

Raf Kinase Inhibitor Protein (RKIP) Dimer Formation Controls Its Target Switch from Raf1 to G Protein-coupled Receptor Kinase (GRK) 2

“…Perturbations within the loop structure were detected in NMR studies with a mutant of RKIP, which at least partially imitates a phosphorylation at this site (RKIP S153E ) (14). Further observations by others strengthen our assumption that this loop represents the interface for RKIP dimerization: loops in general often participate in protein-protein interactions (45,46); particularly, loops with a relatively high fraction of polar, charged residues, as well as glycines and prolines have been suggested to be involved in protein dimerization (37,47). Indeed, loop 127-150 contains eight charged and eight polar amino acids, as well as two glycines and two prolines of 24 amino acids; Banfield et al (8) have generated crystals of dimeric hRKIP and suggested this loop as a putative dimer interface.…”

Amino acid pair- and triplet-wise groupings in the interior of α-helical segments in proteins

“…It has been known for some time that particular sequences of amino acids may have significant roles in protein folding and stability (Nagano, 1973;Nagano, 1974) and, more recent studies have shown how these patterns in pairs in β-sheets, (Fooks et al, 2006) loop sequences, (Crasto and Feng, 2001) particular (i, i + 4) pairs with helix-stabilizing effects (Andrew et al, 2001;Andrew et al, 2002;Butterfield et al, 2002) and dipole-affecting triplets (Iqbalsyah and Doig, 2005a;Olson et al, 2001) may have a stabilizing or destabilizing influence.…”

Empirical potential function for simplified protein models: Combining contact and local sequence–structure descriptors

“…On the other hand, proline has a very rigid side chain and the distribution of its (α, τ ) angles has very limited accessible regions than other amino acid types. These two amino acids are indeed found more frequently in turn/loop conformations among these three secondary structure types (α, β, and turns) [69,70]. The remaining amino acids are clustered into two groups with one group being {ILVYFWCM} and the other group being {DNHSTEKAQR}, which follows roughly their hydrophobicity at the second level of clustering.…”

“…This would affect significantly the geometry of their backbones. Compared with two other similar amino acids, E (Glutamic acid) and Q (Glutamine), D and N are preferred for turn/loop conformations [69,70]. The simplification of amino acids based on local sequencestructure propensities observed in native proteins provides an alternative simplified amino acid alphabet, which will be useful for representation and geometric modeling of protein structures.…”