An automatic procedure for building a protein polyalanine backbone from guiding alpha-carbon positions is presented here,which is different from a previously developed'spare parts'approach(Jones and Thirup,198...An automatic procedure for building a protein polyalanine backbone from guiding alpha-carbon positions is presented here,which is different from a previously developed'spare parts'approach(Jones and Thirup,1986;Claessens et al.,1989). In our procedure,the geometric restraint of angle N-CA-C is used to generate a list of polypeptide chains,and several filters are used later to select the best conformer.The most important filter is based upon the Ramachandran scatter plot of mainchain dihedral angles PHI and PSI.Results for all test cases are satisfactory,with more than 95%of peptide planes correctly reconstructed and the overall root-mean-square deviation less than 0.5 angstrom compared with the refined X-ray coordinates.展开更多
Molecular dynamics simulations are applied to the initial stage of polyalanine13 conformational transi- tion from α-helix to random coil in aqueous environment and the interaction of polyalanine13 with zwitterionic a...Molecular dynamics simulations are applied to the initial stage of polyalanine13 conformational transi- tion from α-helix to random coil in aqueous environment and the interaction of polyalanine13 with zwitterionic and hydrophobic surfaces respectively in the same condition. The analysis of secondary structure, hydrogen bonds, RMSD, dihedral distribution, and the degree of adsorption are performed. The results show that zwitterionic structure maintains the natural behavior of polyalanine13 in water to a better extent, which should be an indirect proof of the hypothesis of "maintain of normal structure."展开更多
A poly-L β-hairpin bent stereochemically as a boat-shaped protein of mixed-L,D structure is scrutinized in basis of ordering as minimum of energy specific for its sequenceand solvent. The model suitable for the scrut...A poly-L β-hairpin bent stereochemically as a boat-shaped protein of mixed-L,D structure is scrutinized in basis of ordering as minimum of energy specific for its sequenceand solvent. The model suitable for the scrutiny is accomplished by design. A terminally-blocked oligoalanine is nucleated overDPro6-Gly7 and DPro6-LAsp7 dipeptide structures as a twelve-residue β-hairpin and bent stereochemically as a boat-shaped fold. The structure is inverse designed with side chains suitable to bind substrate p-nitophenyl phosphate, a surrogate substrate of acetyl choline and CO2. The designed sequences were proven by spectroscopy and molecular dynamics to order with solvent effects of water and display high binding affinity for the substrate. One of the proteins and a cognate oligoalanine are evolved with molecular dynamics to equilibrium in a solvent bath of water. Molecular dynamics studies establish that heteropolypeptide well ordered as β-hairpin fold and cognate oligoalanine as an ensemble of hairpin-like folds in water. The ordering of cognate oligoalanine as ensembles of hairpin-like folds manifests combined role of water as strong dielectric and weak dipolar solvent of peptides. The roles of stereochemistry and chemical details of sequence in defining polypeptides as energy minima under specific effect of solvent are illuminated and have been discussed.展开更多
文摘An automatic procedure for building a protein polyalanine backbone from guiding alpha-carbon positions is presented here,which is different from a previously developed'spare parts'approach(Jones and Thirup,1986;Claessens et al.,1989). In our procedure,the geometric restraint of angle N-CA-C is used to generate a list of polypeptide chains,and several filters are used later to select the best conformer.The most important filter is based upon the Ramachandran scatter plot of mainchain dihedral angles PHI and PSI.Results for all test cases are satisfactory,with more than 95%of peptide planes correctly reconstructed and the overall root-mean-square deviation less than 0.5 angstrom compared with the refined X-ray coordinates.
基金Supported by the National High Technology Research and Development Program of China (Grant No. 2006AA032Z445)the Special program for Key Basic Research of the Ministry of Science and Technology of China (Grant No. 2005CCA00400)+2 种基金the Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20050319010)the Research Foundation of Development and Reform Commission of Jiangsu Province of China (Grant No. 2005103SB9b542)the Research Foundation of Education Bureau of Jiangsu Province of China (Grant Nos. JHjd03-008 and JHB05-21)
文摘Molecular dynamics simulations are applied to the initial stage of polyalanine13 conformational transi- tion from α-helix to random coil in aqueous environment and the interaction of polyalanine13 with zwitterionic and hydrophobic surfaces respectively in the same condition. The analysis of secondary structure, hydrogen bonds, RMSD, dihedral distribution, and the degree of adsorption are performed. The results show that zwitterionic structure maintains the natural behavior of polyalanine13 in water to a better extent, which should be an indirect proof of the hypothesis of "maintain of normal structure."
文摘A poly-L β-hairpin bent stereochemically as a boat-shaped protein of mixed-L,D structure is scrutinized in basis of ordering as minimum of energy specific for its sequenceand solvent. The model suitable for the scrutiny is accomplished by design. A terminally-blocked oligoalanine is nucleated overDPro6-Gly7 and DPro6-LAsp7 dipeptide structures as a twelve-residue β-hairpin and bent stereochemically as a boat-shaped fold. The structure is inverse designed with side chains suitable to bind substrate p-nitophenyl phosphate, a surrogate substrate of acetyl choline and CO2. The designed sequences were proven by spectroscopy and molecular dynamics to order with solvent effects of water and display high binding affinity for the substrate. One of the proteins and a cognate oligoalanine are evolved with molecular dynamics to equilibrium in a solvent bath of water. Molecular dynamics studies establish that heteropolypeptide well ordered as β-hairpin fold and cognate oligoalanine as an ensemble of hairpin-like folds in water. The ordering of cognate oligoalanine as ensembles of hairpin-like folds manifests combined role of water as strong dielectric and weak dipolar solvent of peptides. The roles of stereochemistry and chemical details of sequence in defining polypeptides as energy minima under specific effect of solvent are illuminated and have been discussed.
