Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dynamics of proteins in different solvent systems: analysis of essential motion in lipases.

ABSTRACT: We have investigated the effect of different solvents on the dynamics of Rhizomucor miehei lipase. Molecular dynamics simulations were performed in water, methyl hexanoate, and cyclohexane. Analysis of the 400-ps trajectories showed that the solvent has a pronounced effect on the geometrical properties of the protein. The radius of gyration and total accessibility surface decrease in organic solvents, whereas the number of hydrogen bonds increases. The essential motions of the protein in different solvents can be described in a low-dimensional "essential subspace," and the dynamic behavior in this subspace correlates with the polarity of the solvent. Methyl hexanoate, which is a substrate for R. miehei lipase, significantly increases the fluctuations in the active-site loop. During the simulation, a methyl hexanoate entered the active-site groove. This observation provides insight into the possible docking mechanism of the substrate.

SUBMITTER: Peters GH

PROVIDER: S-EPMC1233717 | biostudies-other | 1996 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Dynamics of proteins in different solvent systems: analysis of essential motion in lipases.

Peters G H GH van Aalten D M DM Edholm O O Toxvaerd S S Bywater R R

Biophysical journal 19961101 5

We have investigated the effect of different solvents on the dynamics of Rhizomucor miehei lipase. Molecular dynamics simulations were performed in water, methyl hexanoate, and cyclohexane. Analysis of the 400-ps trajectories showed that the solvent has a pronounced effect on the geometrical properties of the protein. The radius of gyration and total accessibility surface decrease in organic solvents, whereas the number of hydrogen bonds increases. The essential motions of the protein in differe ...[more]

PMID: 8913568

Similar Datasets

Solvent-induced lid opening in lipases: a molecular dynamics study.

Project description:In most lipases, a mobile lid covers the substrate binding site. In this closed structure, the lipase is assumed to be inactive. Upon activation of the lipase by contact with a hydrophobic solvent or at a hydrophobic interface, the lid opens. In its open structure, the substrate binding site is accessible and the lipase is active. The molecular mechanism of this interfacial activation was studied for three lipases (from Candida rugosa, Rhizomucor miehei, and Thermomyces lanuginosa) by multiple molecular dynamics simulations for 25 ns without applying restraints or external forces. As initial structures of the simulations, the closed and open structures of the lipases were used. Both the closed and the open structure were simulated in water and in an organic solvent, toluene. In simulations of the closed lipases in water, no conformational transition was observed. However, in three independent simulations of the closed lipases in toluene the lid gradually opened. Thus, pathways of the conformational transitions were investigated and possible kinetic bottlenecks were suggested. The open structures in toluene were stable, but in water the lid of all three lipases moved towards the closed structure and partially unfolded. Thus, in all three lipases opening and closing was driven by the solvent and independent of a bound substrate molecule.

| S-EPMC3005783 | biostudies-literature

Organic solvent tolerant lipases and applications.

Project description:Lipases are a group of enzymes naturally endowed with the property of performing reactions in aqueous as well as organic solvents. The esterification reactions using lipase(s) could be performed in water-restricted organic media as organic solvent(s) not only improve(s) the solubility of substrate and reactant in reaction mixture but also permit(s) the reaction in the reverse direction, and often it is easy to recover the product in organic phase in two-phase equilibrium systems. The use of organic solvent tolerant lipase in organic media has exhibited many advantages: increased activity and stability, regiospecificity and stereoselectivity, higher solubility of substrate, ease of products recovery, and ability to shift the reaction equilibrium toward synthetic direction. Therefore the search for organic solvent tolerant enzymes has been an extensive area of research. A variety of fatty acid esters are now being produced commercially using immobilized lipase in nonaqueous solvents. This review describes the organic tolerance and industrial application of lipases. The main emphasis is to study the nature of organic solvent tolerant lipases. Also, the potential industrial applications that make lipases the biocatalysts of choice for the present and future have been presented.

| S-EPMC3929378 | biostudies-other

Solvent-dependent segmental dynamics in intrinsically disordered proteins.

Project description:Protein and water dynamics have a synergistic relationship, which is particularly important for intrinsically disordered proteins (IDPs), although the details of this coupling remain poorly understood. Here, we combine temperature-dependent molecular dynamics simulations using different water models with extensive nuclear magnetic resonance (NMR) relaxation to examine the importance of distinct modes of solvent and solute motion for the accurate reproduction of site-specific dynamics in IDPs. We find that water dynamics play a key role in motional processes internal to "segments" of IDPs, stretches of primary sequence that share dynamic properties and behave as discrete dynamic units. We identify a relationship between the time scales of intrasegment dynamics and the lifetime of hydrogen bonds in bulk water. Correct description of these motions is essential for accurate reproduction of protein relaxation. Our findings open important perspectives for understanding the role of hydration water on the behavior and function of IDPs in solution.

| S-EPMC6598773 | biostudies-literature

Confinement dependence of protein-associated solvent dynamics around different classes of proteins, from the EPR spin probe perspective.

Project description:Protein function is modulated by coupled solvent fluctuations, subject to the degree of confinement from the surroundings. To identify universal features of the external confinement effect, the temperature dependence of the dynamics of protein-associated solvent over 200-265 K for proteins representative of different classes and sizes is characterized by using the rotational correlation time (detection bandwidth, 10-10-10-7 s) of the electron paramagnetic resonance (EPR, X-band) spin probe, TEMPOL, which is restricted to regions vicinal to protein in frozen aqueous solution. Weak (protein surrounded by aqueous-dimethylsulfoxide cryosolvent mesodomain) and strong (no added crysolvent) conditions of ice boundary confinement are imposed. The panel of soluble proteins represents large and small oligomeric (ethanolamine ammonia-lyase, 488 kDa; streptavidin, 52.8 kDa) and monomeric (myoglobin, 16.7 kDa) globular proteins, an intrinsically disordered protein (IDP, β-casein, 24.0 kDa), an unstructured peptide (protamine, 4.38 kDa) and a small peptide with partial backbone order (amyloid-β residues 1-16, 1.96 kDa). Expanded and condensate structures of β-casein and protamine are resolved by the spin probe under weak and strong confinement, respectively. At each confinement condition, the soluble globular proteins display common T-dependences of rotational correlation times and normalized weights, for two mobility components, protein-associated domain, PAD, and surrounding mesodomain. Strong confinement induces a detectable PAD component and emulation of globular protein T-dependence by the amyloid-β peptide. Confinement uniformly impacts soluble globular protein PAD dynamics, and is therefore a generic control parameter for modulation of soluble globular protein function.

| S-EPMC10371532 | biostudies-literature

Accuracy measurement of different marker based motion analysis systems for biomechanical applications: A round robin study.

Project description:IntroductionMultiple camera systems are widely used for 3D-motion analysis. Due to increasing accuracies these camera systems gained interest in biomechanical research areas, where high precision measurements are desirable. In the current study different measurement systems were compared regarding their measurement accuracy.Materials and methodsTranslational and rotational accuracy measurements as well as the zero offset measurements of seven different measurement systems were performed using two reference devices and two different evaluation algorithms. All measurements were performed in the same room with constant temperature at the same laboratory. Equal positions were measured with the systems according to a standardized protocol. Measurement errors were determined and compared.ResultsThe highest measurement errors were seen for a measurement system using active ultrasonic markers, followed by another active marker measurement system (infrared) having measurement errors up to several hundred micrometers. The highest accuracies were achieved by three stereo camera systems, using passive 2D marker points having errors typically below 20 μm.ConclusionsThis study can help to better assess the results obtained with different measurement systems. With the focus on the measurement accuracy, only one aspect in the selection of a system was considered. Depending on the requirements of the user, other factors like measurement frequency, the maximum analyzable volume, the marker type or the costs are important factors as well.

| S-EPMC9273086 | biostudies-literature

Principal component analysis: a method for determining the essential dynamics of proteins.

Project description:It has become commonplace to employ principal component analysis to reveal the most important motions in proteins. This method is more commonly known by its acronym, PCA. While most popular molecular dynamics packages inevitably provide PCA tools to analyze protein trajectories, researchers often make inferences of their results without having insight into how to make interpretations, and they are often unaware of limitations and generalizations of such analysis. Here we review best practices for applying standard PCA, describe useful variants, discuss why one may wish to make comparison studies, and describe a set of metrics that make comparisons possible. In practice, one will be forced to make inferences about the essential dynamics of a protein without having the desired amount of samples. Therefore, considerable time is spent on describing how to judge the significance of results, highlighting pitfalls. The topic of PCA is reviewed from the perspective of many practical considerations, and useful recipes are provided.

| S-EPMC4676806 | biostudies-literature

How a vicinal layer of solvent modulates the dynamics of proteins.

Project description:The dynamics of a folded protein is studied in water and glycerol at a series of temperatures below and above their respective dynamical transition. The system is modeled in two distinct states whereby the protein is decoupled from the bulk solvent at low temperatures, and communicates with it through a vicinal layer at physiological temperatures. A linear viscoelastic model elucidates the less-than-expected increase in the relaxation times observed in the backbone dynamics of the protein. The model further explains the increase in the flexibility of the protein once the transition takes place and the differences in the flexibility under the different solvent environments. Coupling between the vicinal layer and the protein fluctuations is necessary to interpret these observations. The vicinal layer is postulated to form once a threshold for the volumetric fluctuations in the protein to accommodate solvents of different sizes is reached. Compensation of entropic-energetic contributions from the protein-coupled vicinal layer quantifies the scaling of the dynamical transition temperatures in various solvents. The protein adapts different conformational routes for organizing the required coupling to a specific solvent, which is achieved by adjusting the amount of conformational jumps in the surface-group dihedrals.

| S-EPMC2134863 | biostudies-literature

Constant pH molecular dynamics of proteins in explicit solvent with proton tautomerism.

Project description:pH is a ubiquitous regulator of biological activity, including protein-folding, protein-protein interactions, and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH-dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolvation energy of buried charged residues, increasing the error associated with predictions that involve internal ionizable residue that are important in processes like hydrogen transport and electron transfer. Furthermore, discrete water and ions cannot be modeled in implicit solvent, which are important in systems like membrane proteins and ion channels. We report on an explicit solvent constant pH molecular dynamics framework based on multi-site ?-dynamics (CPHMD(MS?D)). In the CPHMD(MS?D) framework, we performed seamless alchemical transitions between protonation and tautomeric states using multi-site ?-dynamics, and designed novel biasing potentials to ensure that the physical end-states are predominantly sampled. We show that explicit solvent CPHMD(MS?D) simulations model realistic pH-dependent properties of proteins such as the Hen-Egg White Lysozyme (HEWL), binding domain of 2-oxoglutarate dehydrogenase (BBL) and N-terminal domain of ribosomal protein L9 (NTL9), and the pKa predictions are in excellent agreement with experimental values, with a RMSE ranging from 0.72 to 0.84 pKa units. With the recent development of the explicit solvent CPHMD(MS?D) framework for nucleic acids, accurate modeling of pH-dependent properties of both major class of biomolecules-proteins and nucleic acids is now possible.

| S-EPMC4394622 | biostudies-literature

Docking glycosaminoglycans to proteins: analysis of solvent inclusion.

Project description:Glycosaminoglycans (GAGs) are anionic polysaccharides, which participate in key processes in the extracellular matrix by interactions with protein targets. Due to their charged nature, accurate consideration of electrostatic and water-mediated interactions is indispensable for understanding GAGs binding properties. However, solvent is often overlooked in molecular recognition studies. Here we analyze the abundance of solvent in GAG-protein interfaces and investigate the challenges of adding explicit solvent in GAG-protein docking experiments. We observe PDB GAG-protein interfaces being significantly more hydrated than protein-protein interfaces. Furthermore, by applying molecular dynamics approaches we estimate that about half of GAG-protein interactions are water-mediated. With a dataset of eleven GAG-protein complexes we analyze how solvent inclusion affects Autodock 3, eHiTs, MOE and FlexX docking. We develop an approach to de novo place explicit solvent into the binding site prior to docking, which uses the GRID program to predict positions of waters and to locate possible areas of solvent displacement upon ligand binding. To investigate how solvent placement affects docking performance, we compare these results with those obtained by taking into account information about the solvent position in the crystal structure. In general, we observe that inclusion of solvent improves the results obtained with these methods. Our data show that Autodock 3 performs best, though it experiences difficulties to quantitatively reproduce experimental data on specificity of heparin/heparan sulfate disaccharides binding to IL-8. Our work highlights the current challenges of introducing solvent in protein-GAGs recognition studies, which is crucial for exploiting the full potential of these molecules for rational engineering.

| S-EPMC3107433 | biostudies-literature

Structural refinement of membrane proteins by restrained molecular dynamics and solvent accessibility data.

Project description:We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (PiO(2)) and nickel-ethylenediaminediacetic acid (PiNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual "solvent" particles corresponding to O(2) and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, "pseudoatom-driven solvent accessibility refinement", was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2-30 A root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1-3 A root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure.

| S-EPMC2586578 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data