Showing papers on "Salt bridge (protein and supramolecular) published in 2003"

Molecular dynamics simulations of pentapeptides at interfaces: Salt bridge and cation-π interactions

Abstract: Peptide−membrane interactions are important for understanding the binding, partitioning, and folding of membrane proteins; the activity of antimicrobial and fusion peptides; and a number of other processes. We describe molecular dynamics simulations (10−25 ns) of two pentapeptides Ace-WLXLL (with X = Arg or Lys side chain) (White, S. H., and Wimley, W.C. (1996) Nat. Struct. Biol. 3, 842−848) in water and three different membrane mimetic systems: (i) a water/cyclohexane interface, (ii) water-saturated octanol, and (iii) a solvated dioleoylphosphatidylcholine bilayer. A salt bridge is found between the protonated Arg or Lys side chains with the carboxyl terminus at the three interfaces. In water/cyclohexane, the salt bridge is most exposed to the water phase and least stable. In water/octanol and the lipid bilayer systems, the salt bridge once formed persists throughout the simulations. In the lipid bilayer, the salt bridge is more stable when the peptide penetrates deeper into the bilayer. In one of two p...

Role of backbone hydration and salt-bridge formation in stability of α-helix in solution

Abstract: We test molecular level hypotheses for the high thermal stability of α-helical conformations of alanine-based peptides by performing detailed atomistic simulations of a 20-amino-acid peptide with explicit treatment of water. To assess the contribution of large side chains to α-helix stability through backbone desolvation and salt-bridge formation, we simulate the alanine-rich peptide, Ac-YAEAAKAAEAAKAAEAAKAF-Nme, referred to as the EK peptide, that has three pairs of "i, i + 3" glutamic acid(-) and lysine(+) substitutions. Efficient configurational sampling of the EK peptide over a wide temperature range enabled by the replica exchange molecular dynamics technique allows characterization of the stability of α-helix with respect to heat-induced unfolding. We find that near ambient temperatures, the EK peptide predominately samples α-helical configurations with 80% fractional helicity at 300 K. The helix melts over a broad range of temperatures with melting temperature, T m , equal to 350 K, that is significantly higher than the T m of a 21-residue polyalanine peptide, A 2 1 . Salt-bridges between oppositely charged Glu - and Lys + side chains can, in principle, provide thermal stability to α-helical conformers. For the specific EK peptide sequence, we observe infrequent formation of Glu-Lys salt-bridges (with ∼10-20% probability) and therefore we conclude that salt-bridge formation does not contribute significantly to the EK peptide's helical stability. However, lysine side chains are found to shield specific "i, i + 4" backbone hydrogen bonds from water, indicating that large side-chain substituents can play an important role in stabilizing α-helical configurations of short peptides in aqueous solution through mediation of water access to backbone hydrogen bonds. These observations have implications on molecular engineering of peptides and biomolecules in the design of their thermostable variants where the shielding mechanism can act in concert with other factors such as salt-bridge formation, thereby increasing thermal stability considerably.

Design and application of basic amino acids displaying enhanced hydrophobicity.

Abstract: Three noncoding basic amino acids, mono-, di-, and trimethyldiaminopropionic acid (mmdap, dmdap, and tmdap), have been synthesized for use in protein design. Covalent modification of a diaminopropionic acid (dap) side chain with an increasing number of methyl moieties results in a family of residues displaying short basic side chains with varying degrees of enhanced hydrophobic character. These residues may be used to introduce charged/polar interactions into the confining hydrophobic interior or interfacial spaces of proteins. As a demonstration of their utility, the ability of these residues to promote interior salt bridge formation at the helix/helix interface of GCN4-p1, a dimeric two-stranded coiled coil, was assessed. Heterodimerization mediated by buried salt bridge formation between a GCN4-based peptide containing either mmdap, dmdap, or tmdap at position 16 and an analogous peptide containing aspartic acid at the same position was studied. Mmdap-derived heterodimers are 0.5 kcal/mol more stable t...

Raman study of the thermal behaviour and conformational stability of basic pancreatic trypsin inhibitor.

Abstract: We have studied the thermal denaturation of native basic pancreatic trypsin inhibitor (BPTI) by monitoring the Raman bands in the 4000–400 cm−1 range. In agreement with results obtained by calorimetry, a cooperative melting transition is observed starting at 75 °C. This transition is found to involve predominantly the unfolding of helical structures accompanied by β-aggregation, loss of hydrophobic interactions between side chains and changes in CSSC dihedral angles. However, salt bridge breaking starts near 40 °C, as deduced from the νs(COO−) band and from the bands close to 1320 and 1345 cm−1 which for the first time have been shown to be due largely to vibrations of the arginine guanidyl group in BPTI. The thermal stability is, hence, attributable to cooperative contributions from hydrophobic and backbone hydrogen bond interactions as well as from disulfide bonds.