scholarly journals Coarse-Grained Free Energy Functions for Studying Protein Conformational Changes: A Double-Well Network Model

2007 ◽  
Vol 93 (11) ◽  
pp. 3860-3871 ◽  
Author(s):  
Jhih-Wei Chu ◽  
Gregory A. Voth
Keyword(s):  
Free Energy ◽  
Network Model ◽  
Conformational Changes ◽  
Coarse Grained ◽  
Energy Functions ◽  
Protein Conformational Changes

scholarly journals SWOTein: a structure-based approach to predict stability Strengths and Weaknesses of prOTEINs

2021 ◽  
Author(s):  
Qingzhen Hou ◽  
Fabrizio Pucci ◽  
François Ancien ◽  
Jean-Marc Kwasigroch ◽  
Raphaël Bourgeas ◽  
...  
Keyword(s):  
Free Energy ◽  
Conformational Changes ◽  
Large Scale ◽  
Hydrogen Exchange ◽  
Test Cases ◽  
Energy Functions ◽  
Functional Regions ◽  
Large Scale Analysis ◽  
The Individual ◽  
Structured Proteins

Abstract Motivation Although structured proteins adopt their lowest free energy conformation in physiological conditions, the individual residues are generally not in their lowest free energy conformation. Residues that are stability weaknesses are often involved in functional regions, whereas stability strengths ensure local structural stability. The detection of strengths and weaknesses provides key information to guide protein engineering experiments aiming to modulate folding and various functional processes. Results We developed the SWOTein predictor which identifies strong and weak residues in proteins on the basis of three types of statistical energy functions describing local interactions along the chain, hydrophobic forces and tertiary interactions. The large-scale analysis of the different types of strengths and weaknesses demonstrated their complementarity and the enhancement of the information they provide. Moreover, a good average correlation was observed between predicted and experimental strengths and weaknesses obtained from native hydrogen exchange data. SWOTein application to three test cases further showed its suitability to predict and interpret strong and weak residues in the context of folding, conformational changes and protein-protein binding. In summary, SWOTein is both fast and accurate and can be applied at small and large scale to analyze and modulate folding and molecular recognition processes. Availability The SWOTein webserver provides the list of predicted strengths and weaknesses and a protein structure visualization tool that facilitates the interpretation of the predictions. It is freely available for academic use at http://babylone.ulb.ac.be/SWOTein/

scholarly journals CGRAP: A Web Server for Coarse-Grained Rigidity Analysis of Proteins

Symmetry ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2401
Author(s):  
Alistair Turcan ◽  
Anna Zivkovic ◽  
Dylan Thompson ◽  
Lorraine Wong ◽  
Lauren Johnson ◽  
...  
Keyword(s):  
Drug Development ◽  
Data Visualization ◽  
Conformational Changes ◽  
Web Server ◽  
Coarse Grained ◽  
Analysis Techniques ◽  
Fine Grained ◽  
Protein Conformational Changes ◽  
Rigidity Analysis ◽  
Rigid Cluster

Elucidating protein rigidity offers insights about protein conformational changes. An understanding of protein motion can help speed drug development, and provide general insights into the dynamic behaviors of biomolecules. Existing rigidity analysis techniques employ fine-grained, all-atom modeling, which has a costly run-time, particularly for proteins made up of more than 500 residues. In this work, we introduce coarse-grained rigidity analysis, and showcase that it provides flexibility information about a protein that is similar in accuracy to an all-atom modeling approach. We assess the accuracy of the coarse-grained method relative to an all-atom approach via a comparison metric that reasons about the largest rigid clusters of the two methods. The apparent symmetry between the all-atom and coarse-grained methods yields very similar results, but the coarse-grained method routinely exhibits 40% reduced run-times. The CGRAP web server outputs rigid cluster information, and provides data visualization capabilities, including a interactive protein visualizer.

Coarse-Grained Molecular Dynamics Simulations of Sugar Transport Across Lactose Permease

2015 ◽  
Author(s):  
Yead Jewel ◽  
Prashanta Dutta ◽  
Jin Liu
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Active Transport ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Sugar Transport ◽  
Potential Of Mean Force ◽  
Coarse Grained ◽  
Lactose Permease ◽  
Protein Conformational Changes

Sugar (one of the critical nutrition elements for all life forms) transport across the cell membranes play essential roles in a wide range of living organism. One of the most important active transport (against the sugar concentration) mechanisms is facilitated by the transmembrane transporter proteins, such as the Escherichia coli lactose permease (LacY) proteins. Active transport of sugar molecules with LacY proteins requires a proton gradient and a sequence of complicated protein conformational changes. However, the exact molecular mechanisms and the protein structural information involved in the transport process are largely unknown. All atom atomistic simulations are able to provide full details but are limited to relative small length and time scales due to the computational cost. The protein conformational changes during sugar transport across LacY are large scale structural reorganization and inaccessible to all atom simulations. In this work, we investigate the molecular mechanisms and conformational changes during sugar transport using coarse-grained molecular dynamics (CGMD) simulations. In our coarse-grained force field, we follow the procedures developed by Han et al. [1, 2], in which the protein model is united-atom based and each heavy atom together with the attached hydrogen atoms is represented by one site, then the protein force filed is coupled with the MARTINI [3] water and lipid force fields. This hybrid force field takes the advantage of the efficiency of MARTINI force field for the environment (water and lipid), while retaining the detailed conformational information for the proteins. Specifically, we develop the new force fields for interactions between sugar molecules and protein by matching the potential of mean force between all-atom and coarse-grained models. Then we validate our force field by comparing the potential of mean force for a glucose interaction with a carbohydrate binding protein from our new force field, with the results from all atom simulations. After validation, we implement the force field for sugar transport across LacY proteins. Through our simulations we are able to capture the formation/breakage of the important hydrogen bonds and salt bridges, which are crucial to the overall conformational changes of LacY.

Current understanding of the function of magnesium chelatase

2002 ◽  
Vol 30 (4) ◽  
pp. 643-645 ◽  
Author(s):  
J. D. Reid ◽  
C. N. Hunter
Keyword(s):  
Free Energy ◽  
Branch Point ◽  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Current Understanding ◽  
Biosynthetic Pathways ◽  
Magnesium Chelatase ◽  
Functional Studies ◽  
Protein Conformational Changes ◽  
Key Enzyme

Despite the global significance of chlorophylls and other modified tetrapyrroles, many aspects of their biosynthetic pathways are poorly understood. A key enzyme at the branch point between the haem and chlorophyll pathways, magnesium chelatase, couples the free energy of ATP hydrolysis to the insertion of magnesium into porphyrin, a process that is likely to be mediated through protein conformational changes. Conclusions from recent structural and functional studies of individual subunits are combined to provide a mechanistic outline of the full magnesium chelatase complex. Gathering further information presents a considerable challenge, and recent steps towards this goal will be introduced.

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