scholarly journals Accurate Three States Model for Amino Acids with Two Chemically Coupled Titrating Sites in Explicit Solvent Atomistic Constant pH Simulations and pKa Calculations

2016 ◽  
Vol 13 (1) ◽  
pp. 147-160 ◽  
Author(s):  
Plamen Dobrev ◽  
Serena Donnini ◽  
Gerrit Groenhof ◽  
Helmut Grubmüller
Keyword(s):  
Amino Acids ◽  
Pka Calculations ◽  
Constant Ph ◽  
Explicit Solvent

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

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

2014 ◽  
Vol 82 (7) ◽  
pp. 1319-1331 ◽  
Author(s):  
Garrett B. Goh ◽  
Benjamin S. Hulbert ◽  
Huiqing Zhou ◽  
Charles L. Brooks
Keyword(s):  
Molecular Dynamics ◽  
Constant Ph ◽  
Explicit Solvent ◽  
Constant Ph Molecular Dynamics

Thermodynamics of Helix formation in small peptides of varying lengthin vacuo, implicit solvent and explicit solvent: Comparison between AMBER force fields

2019 ◽  
Vol 18 (03) ◽  
pp. 1950015
Author(s):  
Zhaoxi Sun ◽  
Xiaohui Wang
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Hydrogen Bonds ◽  
Force Fields ◽  
Implicit Solvent ◽  
Conformational Ensemble ◽  
Helix Formation ◽  
Solvent Models ◽  
Explicit Solvent ◽  
Amber Force Fields

Helix formation is of great significance in protein folding. The helix-forming tendencies of amino acids are accumulated along the sequence to determine the helix-forming tendency of peptides. Computer simulation can be used to model this process in atomic details and give structural insights. In the current work, we employ equilibrate-state free energy simulation to systematically study the folding/unfolding thermodynamics of a series of mutated peptides. Two AMBER force fields including AMBER99SB and AMBER14SB are compared. The new 14SB force field uses refitted torsion parameters compared with 99SB and they share the same atomic charge scheme. We find that in vacuo the helix formation is mutation dependent, which reflects the different helix propensities of different amino acids. In general, there are helix formers, helix indifferent groups and helix breakers. The helical structure becomes more favored when the length of the sequence becomes longer, which arises from the formation of additional backbone hydrogen bonds in the lengthened sequence. Therefore, the helix indifferent groups and helix breakers will become helix formers in long sequences. Also, protonation-dependent helix formation is observed for ionizable groups. In 14SB, the helical structures are more stable than in 99SB and differences can be observed in their grouping schemes, especially in the helix indifferent group. In solvents, all mutations are helix indifferent due to protein–solvent interactions. The decrease in the number of backbone hydrogen bonds is the same with the increase in the number of protein–water hydrogen bonds. The 14SB in explicit solvent is able to capture the free energy minima in the helical state while 14SB in implicit solvent, 99SB in explicit solvent and 99SB in implicit solvent cannot. The helix propensities calculated under 14SB agree with the corresponding experimental values, while the 99SB results obviously deviate from the references. Hence, implicit solvent models are unable to correctly describe the thermodynamics even for the simple helix formation in isolated peptides. Well-developed force fields and explicit solvents are needed to correctly describe the protein dynamics. Aside from the free energy, differences in conformational ensemble under different force fields in different solvent models are observed. The numbers of hydrogen bonds formed under different force fields agree and they are mostly determined by the solvent model.

scholarly journals Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides

2020 ◽  
Vol 16 (4) ◽  
pp. 2561-2569 ◽  
Author(s):  
Plamen Dobrev ◽  
Sahithya Phani Babu Vemulapalli ◽  
Nilamoni Nath ◽  
Christian Griesinger ◽  
Helmut Grubmüller
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Constant Ph ◽  
Explicit Solvent ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics

scholarly journals Application of Explicit-Solvent Constant ph Molecular Dynamics to Proteins

2013 ◽  
Vol 104 (2) ◽  
pp. 508a
Author(s):  
Wei Chen ◽  
Jason A. Wallace ◽  
Zhi Yue ◽  
Jana K. Shen
Keyword(s):  
Molecular Dynamics ◽  
Constant Ph ◽  
Explicit Solvent ◽  
Constant Ph Molecular Dynamics

Isodesmic reaction for accurate theoretical pKa calculations of amino acids and peptides

2016 ◽  
Vol 18 (16) ◽  
pp. 11202-11212 ◽  
Author(s):  
S. Sastre ◽  
R. Casasnovas ◽  
F. Muñoz ◽  
J. Frau
Keyword(s):  
Amino Acids ◽  
Computational Chemistry ◽  
Computational Cost ◽  
Quantitative Prediction ◽  
Isodesmic Reaction ◽  
Pka Calculations ◽  
Current Challenge ◽  
Low Computational Cost ◽  
A Current

Theoretical and quantitative prediction of pKa values at low computational cost is a current challenge in computational chemistry.

scholarly journals Explicit solvent models in protein pKa calculations

1996 ◽  
Vol 71 (1) ◽  
pp. 138-147 ◽  
Author(s):  
C.J. Gibas ◽  
S. Subramaniam
Keyword(s):  
Pka Calculations ◽  
Solvent Models ◽  
Explicit Solvent ◽  
Protein Pka
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