Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 7527150

Multiple copy sampling: rigid versus flexible protein.

Q Zheng·D J Kyle
View original source ↗Export metadata ↓

Abstract

Effects of protein flexibility on multiple copy conformational sampling were systematically evaluated by studying the side-chain placement of Phe-14 in protein Zif268. The multiple copy sampling is shown to be significantly more efficient when a flexible but harmonically constrained protein is used instead of a rigid protein. A range of constraint force from 1 to 25 kcal/mol.A per atom is determined to be sufficient to prevent the protein from distortion while allowing the protein to fluctuate for enhanced sampling. The protein fluctuations are essential in smoothing the effective energy surface as shown by the opening-closing of a protein hydrophobic pocket during a multiple copy energy minimization, a phenomenon that has been previously observed only in molecular dynamics. These results provide a practical guidance for applying the multiple copy techniques to molecular modeling and computer-aided drug design.

Explore related subjects

AprotininComputer SimulationDNA-Binding ProteinsDrug DesignKallikreinsModels, MolecularProtein ConformationTranscription FactorsZinc FingersJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Q Zheng, D J Kyle. 1994. Multiple copy sampling: rigid versus flexible protein.. https://doi.org/10.1002/prot.340190407

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Ultra-low dose aprotinin effects on reducing the need for blood transfusion in cardiac surgery.

OBJECTIVE: To assess the effects of ultra-low dose one million kallikrein inhibitor units (KIU) of aprotinin on bleeding and the need for transfusion after cardiac surgery. METHODS: We carried out this randomized clinical trial on 162 cardiac surgery patients in Shahid Madani Hospital, Tabriz, Iran from April 2004 to December 2005. The patients were randomly divided into 2 groups of 81 individuals. In the aprotinin group, 0.5 million KIU infused before and 0.5 million KIU during cardiopulmonary bypass. In the placebo group, 100 ml normal saline was infused as above. The need to use fresh frozen plasma (FFP), packed red blood cells (PRBCs) transfusion during, after operation, the rate of chest tubes drainage at 6, 12 and 24 hours after surgery were measured in 2 groups. RESULTS: Chest tubes drainage at 6 hours after surgery was 190 +/- 24 ml in the aprotinin group and 266 +/- 33 ml in the placebo group (p=0.066). The amount of bleeding at 12 and 24 hours was significantly different between 2 groups (p=0.048, p=0.009). The frequency of blood products transfusion in the aprotinin group was 68% and in the placebo group was 75% (p=0.02). The number of PRBCs and FFP units transfused were significantly lower in the aprotinin group (p=0.000, p=0.005). Total amount of blood and products transfusion in the aprotinin group was 2.56 +/- 0.27 units and in placebo group it was 4.37 +/- 0.27 units (p=0.0001). CONCLUSION: Results indicate that the use of one million KIU of aprotinin in cardiac surgery is effective in reducing postoperative bleeding and transfusion requirements.

Aprotinin↗
PubMed2006

Aprotinin; friend or foe? A review of recent medical literature.

Recent articles published in peer review journals have questioned the safety of using aprotinin in patients having heart surgery. Also, evidence has been published to suggest an increase in renal events in patients given aprotinin when compared to those where tranexamic acid was used. The present review will focus principally on the first of these articles in relation to previously published data and experience.

Aprotinin↗