RRC ID 61579
Author Ohkura K.
Title Exploring unique structures: flexibility is a significant factor in biological activity.
Journal Biol Pharm Bull
Abstract The effect of molecular flexibility on biological activity was described for soft (e.g. hGH peptides) and hard molecules (e.g. biscoclaurine-type alkaloids). These molecules had a macrocyclic structure during molecular mechanics analysis, and the minimum essential unit, which affects insulin-involved fatty acid synthesis, was observed. The flexibility of the molecular center is concerning with biological activity through the diversification of structural feature, and compared with two types of molecules which have a rigid (haloacetylcarbamoyl-2-nitroimidazole analogs: chiral-TXs) or flexible (bis-quaternary ammonium compounds: bis-QACs) molecular center. Center flexibility reflected the conformation occurrence in TXs and bis-QACs. A parameter (solvation-free energy: dGW), which reflects structural hydrophobicity, was shown, and applied to the molecular design of brefeldin A analog. This hydrophobic index was very useful, and was used for conformational analysis of chiral-TXs and bis-QACs. In molecular dynamics analysis of cholesterol-dependent cytolysin (e.g. streptolysin O) and -independent cytolysin (e.g. intermedilysin), whole molecules moved like a bow and different conformations were shown in every moment. In such situations, the membrane-associated 11mer region in these cytolysins were flexible and could always interact with extramolecular factors (e.g. membrane constitution).
Volume 30(6)
Pages 1025-36
Published 2007-6-1
DOI 10.1248/bpb.30.1025
PII JST.JSTAGE/bpb/30.1025
PMID 17541149
MeSH Amino Acid Sequence Animals Computer Simulation Humans Hydrophobic and Hydrophilic Interactions Molecular Conformation Molecular Structure Peptides / chemistry Protein Binding Protein Conformation* Protein Structure, Secondary Protein Structure, Tertiary Stereoisomerism Structure-Activity Relationship Thermodynamics
IF 1.54
Human and Animal Cells NB1RGB(RCB0222)