Unambiguous Assignment of Reduction Potentials in Diheme Cytochromes

Coupled redox and pH-driven processes are at the core of many important biological mechanisms.As the distribution of protonation and redox states in a system is associated with the pH and redox potential of the solution, having efficient computational tools that can simulate under these conditions become very important. Such tools have the potential to provide information that complement and drive experiments. In previous publications we have presented the implementation of the constant pH and redox potential molecular dynamics (C(pH,E)MD) method in AMBER and we have shown how multidimensional replica exchange can be used to significantly enhance the convergence efficiency of our simulations. In the current work, after an improvement in our C(pH,E)MD approach that allows a given residue to be simultaneously pHand redox-active, we have employed our methodologies to study five different systems of interest in the literature. We present results for: capped tyrosine dipeptide, two maquette systems containing one pH-and redox-active tyrosine (α 3 Y and peptide A), and two proteins that contain multiple heme groups (diheme cytochrome c from Rhodobacter sphaeroides and Desulfovibrio vulgaris Hildenborough cytochrome c 3 ). We show that our results can provide new insights into previous theoretical and experimental findings by using a fully force field-based and GPUaccelerated approach, which allows the simulations to be executed with high computational performance.

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confidence: 99%

Exploring Coupled Redox and pH Processes with a Force-Field-Based Approach: Applications to Five Different Systems

2020

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“…Previous CpHMD publications using AMBER45 have already shown to under or overestimate pK a values by 1 unit or more, and such inaccuracy would certainly affect our ΔE o predictions.Our E,pH-REMD simulations clearly assign the experimental E o values of -240 and -310 mV respectively to the Nter heme and the Cter heme. This conclusion is in disagreement with a previous theoretical study performed by Daidone et al47 in which the opposite assignment was concluded. Regardless of any limitations that the theoretical approach used by Daidone et al might have, it is important to notice that in their simulations the protonation state of all pH-active residues was kept constant, however, as our E,pH-REMD simulations show, many pH-active residues titratable at pH 7.5, including the heme propionates, and this effect is certainly important for the proper description of the E o values.…”

contrasting

confidence: 99%

Exploring Coupled Redox and pH Processes with a Force Field-Based Approach: Applications to Five Different Systems

Cruzeiro¹,

Feliciano²,

Roitberg

2020

Preprint

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Coupled redox and pH-driven processes are at the core of many important biological mechanisms. As the distribution of protonation and redox states in a system is associated with the pH and redox potential of the solution, having efficient computational tools that can simulate under these conditions become very important. Such tools have the potential to provide information that complement and drive experiments. In previous publications we have presented the implementation of the constant pH and redox potential molecular dynamics (C(pH,E)MD) method in AMBER and we have shown how multidimensional replica exchange can be used to significantly enhance the convergence efficiency of our simulations. In the current work, after an improvement in our C(pH,E)MD approach that allows a given residue to be simultaneously pH- and redox-active, we have employed our methodologies to study five different systems of interest in the literature. We present results for: capped tyrosine dipeptide, two maquette systems containing one pH- and redox-active tyrosine (α3Y and peptide A), and two proteins that contain multiple heme groups (diheme cytochrome c from Rhodobacter sphaeroides and Desulfovibrio vulgaris Hildenborough cytochrome c3). We show that our results can provide new insights into previous theoretical and experimental findings by using a fully force field-based and GPUaccelerated approach, which allows the simulations to be executed with high computational performance.

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“…By such an approach, the free energy of several molecular processes—including redox potentials—in realistic environments have been modeled so far [ 16 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

Section: Theoretical-computational Approachesmentioning

confidence: 99%

Theoretical Modeling of Redox Potentials of Biomolecules

et al. 2022

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The estimation of the redox potentials of biologically relevant systems by means of theoretical-computational approaches still represents a challenge. In fact, the size of these systems typically does not allow a full quantum-mechanical treatment needed to describe electron loss/gain in such a complex environment, where the redox process takes place. Therefore, a number of different theoretical strategies have been developed so far to make the calculation of the redox free energy feasible with current computational resources. In this review, we provide a survey of such theoretical-computational approaches used in this context, highlighting their physical principles and discussing their advantages and limitations. Several examples of these approaches applied to the estimation of the redox potentials of both proteins and nucleic acids are described and critically discussed. Finally, general considerations on the most promising strategies are reported.

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Unambiguous Assignment of Reduction Potentials in Diheme Cytochromes

Cited by 23 publications

References 69 publications

Exploring Coupled Redox and pH Processes with a Force-Field-Based Approach: Applications to Five Different Systems

Exploring Coupled Redox and pH Processes with a Force-Field-Based Approach: Applications to Five Different Systems

Exploring Coupled Redox and pH Processes with a Force Field-Based Approach: Applications to Five Different Systems

Theoretical Modeling of Redox Potentials of Biomolecules

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