Origin of the different strengths of the (i,i+4) and (i,i+3) leucine pair interactions in helices.
Pairs of leucine side chains, spaced either (i,i+3) or (i,i+4), are known to stabilize alanine-based peptide helices, Experiments with new peptide sequences confirm that the (i,i+4) pair interaction is markedly stronger than the (i,i+3) pair interaction. This result is not expected from reported Monte Carlo simulations, which predict that the (i,i+3) interaction is slightly stronger. The interaction strength can be predicted from recently reported measurements of buried non-polar surface area, obtained from structures in the Protein Data Bank: the agreement is reasonable for the (i,i+3) LL interaction but underestimates the (i,i+4) LL interaction. Solvation of peptide groups in the helix backbone may contribute to the different strengths of the two LL pair interactions because different chi(1) leucine rotamers are used and the (i,i+3) pair shields two peptide groups whereas the (i,i+4) pair shields only one. A rough estimate of the backbone solvation effect, based on the difference between the helix propensities of leucine and alanine, agrees with the size of the difference between the (i,i+3) and (i,i+4) leucine pair interactions.
Luo
Peizhi
P
Department of Biochemistry, Beckman Center, Stanford University Medical Center, Stanford, CA 94305-5307, USA.
Baldwin
Robert L
RL
D002942:Circular Dichroism; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012997:Solvents / Q000494:pharmacology; D013696:Temperature; D013816:Thermodynamics
D010455:Peptides; D012997:Solvents; D007930:Leucine