PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11746690

Classical molecular interaction potentials: improved setup procedure in molecular dynamics simulations of proteins.

J L Gelpí·S G Kalko·X Barril·J Cirera·X de La Cruz·F J Luque·M Orozco
View original source ↗Export metadata ↓

Abstract

The latest version of the classical molecular interaction potential (CMIP) has the ability to predict the position of crystallographic waters in several proteins with great accuracy. This article analyzes the ability of the CMIP functional to improve the setup procedure of the molecular system in molecular dynamics (MD) simulations of proteins. To this end, the CMIP strategy is used to include both water molecules and counterions in different protein systems. The structural details of the configurations sampled from trajectories obtained using the CMIP setup procedure are compared with those obtained from trajectories derived from a standard equilibration process. The results show that standard MD simulations can lead to artifactual results, which are avoided using the CMIP setup procedure. Because the CMIP is easy to implement at a low computational cost, it can be very useful in obtaining reliable MD trajectories.

Explore related subjects

AcetylcholinesteraseAnimalsBinding SitesCatalaseComputer SimulationHumansIonsModels, ChemicalMotionProtein ConformationProteinsStatic ElectricityThymidine KinaseWaterJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J L Gelpí, S G Kalko, X Barril, J Cirera, X de La Cruz, F J Luque, M Orozco. 2001-12-01. Classical molecular interaction potentials: improved setup procedure in molecular dynamics simulations of proteins.. https://doi.org/10.1002/prot.1159

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

KEEP EXPLORING

Related citations

PubMed2002

Transcriptional regulation of gene expression by the coding sequence: An attempt to enhance expression of human AChE.

In a previous report, Morel and Massoulié showed that Bungarus AChE (bBAChE) is produced more efficiently than rat AChE in various expression systems, mainly because the Bungarus coding sequence exerts a stimulatory effect on transcription (Morel and Massoulié, 2000). They reported that a 5' Bungarus fragment could partially transfer this property to a CAT expression vector. This appeared to offer the possibility of increasing the production of recombinant proteins. In the present paper, we show that insertion of this fragment in the transcribed region, before the polyadenylation site, may have either stimulatory or inhibitory effects, depending on the vector and on the reporter gene. Since the stimulatory effect of Bungarus coding region could not be attached to a small number of discrete motifs, we reasoned that it might result from a general feature of the sequence. Therefore it might be possible to partially transfer this property to the very homologous human AChE (hHAChE) coding sequence by modifications based on synonymous codons, which increased nucleotide identity between the 5' fragment (721 nucleotides) of bBAChE and hHAChE from 71% to 85%. The production of human AChE in transfected COS cells was increased nearly 2-fold with this modified construct, but still remained about 4-fold smaller than that of Bungarus AChE. There was no change in expression level in transformed Pichia pastoris. We thus confirm that coding sequences can strongly influence gene expression, but in a manner that depends on the context and cannot yet be predicted.

Acetylcholinesterase↗
PubMed2002

Rapid assessment of organophosphorous/carbamate exposure in the bivalve mollusc Mytilus edulis using combined esterase activities as biomarkers.

Carboxylesterases in bivalve molluscs exhibit greater sensitivity to organophosphorous and carbamate pesticides than acetylcholinesterase and are present at higher levels. The aim of the present study was to combine measurement of both acetylcholinesterase and carboxylesterase activities in the marine bivalve Mytilus edulis in order to detect the effects of pesticide exposure. Spectrophotometric assays in microtitreplate format were optimised for use with M. edulis haemolymph and tissue homogenate samples. This permitted the nature and distribution of the enzymes to be determined. One predominant pharmacological form of activity consistent in its patterns of activation and inhibition with acetylcholinesterase was identified in the haemolymph with an apparent K(m) for acetylthiocholineiodide of 1.33 mM. Carboxylesterase activity in the tissues was characterised by its preferential hydrolysis of the substrate analogue phenylthioacetate. Concentration-dependent inhibition of both activities was demonstrated following in vitro incubation with diisopropylfluorophosphate (DFP), paraoxon and eserine in the range 0.1-3.0 mM. When M. edulis (n=10) were exposed for 24 h to concentrations of eserine or paraoxon of 0.05-1.0 mM, the percentage inhibition of acetylcholinesterase was in each case greater than for carboxylesterase and reached statistical significance at lower concentrations. In all exposures, a proportion of carboxylesterase activity was present which remained resistant to inhibition by either organophosphorous or carbamate compounds. The ecotoxicological significance of these findings for the environmental monitoring of pesticide exposure is discussed.

Acetylcholinesterase↗
PubMed2002

Cell surface expression of a GPI-anchored form of mouse acetylcholinesterase in Klpmr1Delta cells of Kluyveromyces lactis.

The mouse acetylcholinesterase AChE(H) was expressed in the yeast Kluyveromyces lactis. The AChE(H) activity was detectable in intact cells whereas it was absent in the culture media. Glucanase treatment and immunoelectron microscopy data indicated that AChE(H) is anchored to plasma membrane and that the mouse GPI-signaling is compatible with the K. lactis targeting machinery. The AChE(H) was also expressed in a K. lactis strain carrying an inactivated allele of KlPMR1, the gene coding for a P-type Ca(2+)-ATPase of the Golgi apparatus. This mutant displays changes in protein glycosylation and cell wall structure. The AChE(H) activity detected in Klpmr1Delta cells was more than twofold higher than that observed in wild-type cells. The combination of AChE expression and anchoring with the characteristics of Klpmr1Delta strain of K. lactis resulted in yeast cells displaying high AChE activity. This could be regarded as a novel sensing unit to be employed for detecting AChE inhibitors as pesticides.

Acetylcholinesterase↗