Topics

Accurate Calculation of Barnase and SNase Folding Energetics using short MD simulations and an Atomistic Model of the Unfolded Ensemble. Evaluation of Force Fields and Water Models.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Accurate Calculation of Barnase and SNase Folding Energetics using short MD simulations and an Atomistic Model of the Unfolded Ensemble. Evaluation of Force Fields and Water Models."

As proteins perform most cellular functions, quantitative understanding of protein energetics is required to gain control of biological phenomena. Accurate models of native proteins can be obtained experimentally but the lack of equally fine models of unfolded ensembles impedes the calculation of protein folding energetics from first principles. Here we show that an atomistic unfolded ensemble model, consisting on a few dozen conformations built from a protein sequence, can be used in conjunction with an X-ray structure of its native state to calculate accurately by difference the changes in enthalpy and in heat capacity of the polypeptide upon folding. The calculation is done using Molecular Dynamics simulations and popular force fields and water models and, for the two model proteins studied (barnase and SNase), the results agree within error or are very close to their experimentally determined properties. The enthalpy sampling of the unfolded ensemble is done through short 2-ns simulations that do not significantly modify the representative distribution of Rg of the starting conformations. The impressive accuracy obtained opens the possibility to investigate quantitatively systems or phenomena not amenable to experiment, and paves the way for addressing the calculation of protein conformational stability (i.e. the change in Gibbs energy upon folding), a central goal of Structural Biology. So far, these calculated enthalpy and heat capacity changes, combined with the experimentally determined melting temperatures of the corresponding protein, allow to reproduce the stability curves of both barnase and SNase.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of chemical information and modeling
ISSN: 1549-960X
Pages:

Links

DeepDyve research library

PubMed Articles [8009 Associated PubMed Articles listed on BioPortfolio]

Effective hybrid approach for protein structure prediction in a two-dimensional Hydrophobic-Polar model.

Hydrophobic-polar (HP) models are widely used to predict protein folding and hydrophobic interactions. Numerous optimization algorithms have been proposed to predict protein folding using the two-dime...

A novel folding pathway of the villin headpiece subdomain HP35.

The villin headpiece subdomain (HP35) is a fast-folding protein with 35 residues and its folding pathways have been extensively studied experimentally and theoretically but remain controversial. While...

Towards high-precision calculation of electron capture decays.

Based on previous study, the calculation of electron capture decays has been improved by considering a more accurate atomic model with precise atomic energies, and different radiative corrections have...

Protein polymerization in dumpling wrappers influenced by folding patterns.

The influences of folding patterns on the protein polymerization in dumpling wrappers were investigated. The dumpling dough sheet after the compounding rollers was folded with various patterns (contro...

Parallel G-triplexes and G-hairpins as potential transitory ensembles in the folding of parallel-stranded DNA G-Quadruplexes.

Guanine quadruplexes (G4s) are non-canonical nucleic acids structures common in important genomic regions. Parallel-stranded G4 folds are the most abundant, but their folding mechanism is not fully un...

Clinical Trials [3407 Associated Clinical Trials listed on BioPortfolio]

Parental Blinding in Clinical Trials of Osteopathy

The aim of this research is to assess the acceptability of using a mobile folding screen for blinding parents of infant study participants in clinical trials of osteopathic interventions. ...

Comparative Study of Three IOL Power Calculation Formulae for Asian Eyes Shorter Than 22mm or Longer Than 25mm

Implantation of an intraocular lens is the gold standard in modern day cataract surgery. The appropriate lens power needed to achieve the desired refractive outcome can be calculated with...

Adjusted Calculation of Heparin and Protamin Dosing and Correlation With Postoperative Bleeding and Transfusions

The study will compare a novel calculation model (HeProCalc AB) with a standard weight-based and activated clotting time adjusted calculation for the dosing of Heparin and protamine and as...

Improving Assessment (and Ultimately Outcomes) of Permanent Prostate Implant Therapy

Permanent prostate implants are a type of radiation therapy in which a high dose of radiation is delivered to cancerous tissue by many small radioactive "seeds". Studies of early-stage pr...

Intraocular Lens Power Calculation for Combined Phaco-vitrectomy Procedures

The aim of the study is to evaluate the degree of refractive error postoperatively in combined procedures and to calculate a new constant in order to improve current state of the art biome...

Medical and Biotech [MESH] Definitions

The planning, calculation, and creation of an apparatus for the purpose of correcting the placement or straightening of teeth.

Calculation of the energy expenditure in the form of heat production of the whole body or individual organs based on respiratory gas exchange.

Procedures for collecting, preserving, and transporting of specimens sufficiently stable to provide accurate and precise results suitable for clinical interpretation.

A visual image which is recalled in accurate detail. It is a sort of projection of an image on a mental screen.

A genus of hamsters characterized by small size, very short tail, and short, broad feet with hairy soles.

Quick Search


DeepDyve research library

Relevant Topics

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...


Searches Linking to this Article