Conformational templates for rational drug design: flexibility of cyclo(D-Pro1-Ala2-Ala3-Ala4-Ala5) in DMSO solution.
Long MD simulations (100 ns) for the important model cyclopentapeptide cyclo(D-Pro1-Ala2-Ala3-Ala4-Ala5) were performed in explicit DMSO solution using both OPLS-AA and AMBER03 force fields. Simulations revealed conformational transitions between two main conformers, a predominant one (population 93-99%) and a minor conformer (population 0.4-6.7%). These results are in excellent agreement with 20 experimental proton-proton distances estimated for this cyclopentapeptide. The previously discussed gamma-turn-like conformation for Ala4 was present only in a minor conformer.
Zhang
Xiaoming
X
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nikiforovich
Gregory V
GV
Marshall
Garland R
GR
D004121:Dimethyl Sulfoxide; D015195:Drug Design; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D013816:Thermodynamics
D010456:Peptides, Cyclic; D012996:Solutions; C407429:cyclo(prolyl-alanyl-alanyl-alanyl-alanyl); D004121:Dimethyl Sulfoxide